Groups of Borrelia burgdorferi and Borrelia afzelii that cause Lyme Disease in humans

Abstract

The present invention is drawn to an immunogenic composition comprising OspC polypeptides from Lyme Disease causing Borrelia. In one embodiment, the immunogenic composition of the present invention comprises at least one OspC polypeptide or immunogenic fragment thereof from each of Borrelia burgdorferi OspC families A, B, I and K. In another embodiment, the immunogenic composition of the present invention comprises at least one OspC polypeptide or immunogenic fragment thereof from each of Borrelia afzelii OspC families A and B.

Claims

What is claimed is:

1. A method of immunizing an animal against Lyme disease, comprising administering a composition comprising at least two OspC polypeptides from Lyme Disease causing Borrelia wherein said composition comprises one or more OspC polypeptides from at least two Borrelia burgdorferi sensu stricto OspC families selected from the group consisting of: A, B, I and K, excepting the combination consisting of two OspC proteins wherein one OspC protein is from OspC family A and the second OspC protein is from OspC family I.

2. The method of claim 1, wherein the composition comprises one or more OspC polypeptides from each Borrelia burgdorferi sensu stricto family.

3. The method of claim 1, wherein said OspC polypeptide comprises the OspC protein variable region.

4. The method of claim 1, wherein one of the OspC polypeptide is encoded by a nucleic acid comprising nucleotide 26 to about nucleotide 621 of an ospC gene from a Borrelia burgdorferi sensu stricto family selected from the group consisting of: A, B, I and K.

5. The method of claim 1, wherein one of the OspC polypeptides is encoded by a nucleic acid comprising nucleotide 53 to about nucleotide 570 of an ospC gene from a Borrelia burgdorferi sensu stricto family selected from the group consisting of: A, B, I and K.

6. The method of claim 1, wherein at least two of said OspC polypeptides are fused together in a single protein, encoded by a single nucleic acid, wherein polypeptides in said fusion protein are not found in the same configuration in a naturally occurring OspC protein.

7. The method of claim 1, wherein the ospC gene encoded the OspC polypeptides within a given OspC family are at least 98% identical at the nucleic acid level.

8. The method of claim 1, wherein Borrelia burgdorferi sensu stricto OspC family A comprises strains B31, CA4, HII, IPI, IP2, IP3, L5, PIF, Pka, Txgw and strains containing ospC allele OC1.

9. The method of claim 1, wherein Borrelia burgdorferi sensu stricto OspC family B comprises strains 35B808, 61 BV3, BUR, DK7, PB3, Z57 and strains containing ospC genes OC2 and OC3.

10. The method of claim 1, wherein Borrelia burgdorferi sensu stricto OspC family I comprises strains 297, HB19 and strains containing ospC gene OC10, wherein strain 297 is characterized by ospC of GenBank accession number L42893 (SEQ ID NO:85).

11. The method of claim 1, wherein Borrelia burgdorferi sensu stricto OspC family K comprises strains 272, 297, 28354, KIPP, MUL and strains containing ospC gene OC12 and OC13, wherein strain 297 is characterized by ospC of GenBank accession number U08284 (SEQ ID NO:86).

12. A method of detecting an immune response to Lyme Disease causing Borrelia in a host sample, comprising; a) contacting the host sample with a composition comprising OspC polypeptides from Lyme disease causing strains of Borrelia, such that anti-OspC antibodies, if present in said sample bind to said OspC polypeptides; wherein said composition comprises one or more OspC polypeptides from at least two Borrelia burgdorferi sensu stricto OspC families selected from the group consisting of: A, B, I and K, excepting the combination consisting of two OspC proteins wherein one OspC proteins is from family A and the second OspC protein is from family I, and b) detecting antibodies that have bound said OspC peptides; thereby detecting an immune response to Lyme disease causing Borrelia.

13. The method of claim 12, wherein said OspC polypeptide comprises the OspC protein variable region.

14. The method of claim 12, wherein one of the OspC polypeptide is encoded by a nucleic acid comprising nucleotide 26 to about nucleotide 621 of an ospC gene from a Borrelia burgdorferi sensu stricto family selected from the group consisting of: A, B, I and K.

15. The method of claim 12, wherein one of the OspC polypeptides is encoded by a nucleic acid comprising nucleotide 53 to about nucleotide 570 of an ospC gene from a Borrelia burgdorferi sensu stricto family selected from the group consisting of: A, B, I and K.

16. The method of claim 12, wherein at least two of said OspC polypeptides are fused together in a single protein, encoded by a single nucleic acid, wherein polypeptides in said fusion protein are not found in the same configuration in a naturally occurring OspC protein.

17. The method of claim 12, wherein the ospC genes encoding the OspC polypeptides within a given OspC family are at least 98% identical at the nucleic acid level.

18. The method of claim 17, wherein Borrelia burgdorferi sensu stricto OspC family A comprises strains B31, CA4, HII, IPI, IP2, IP3, L5, PIF, Pka, Txgw and strains containing ospC allele OC1.

19. The method of claim 17, wherein Borrelia burgdorferi sensu stricto OspC family B comprises strains 35B808, 61 BV3, BUR, DK7, PB3, Z57 and strains containing ospC genes OC2 and OC3.

20. The method of claim 17, wherein Borrelia burgdorferi sensu stricto OspC family I comprises strains 297, HB19 and strains containing ospC gene OC10, wherein strain 297 is characterized by ospC of GenBank accession number L42893 (SEQ ID NO:85).

21. The method of claim 17, wherein Borrelia burgdorferi sensu stricto OspC family K comprises strains 272, 297, 28354, KIPP, MUL and strains containing ospC gene OC12 and OC13, wherein strain 297 is characterized by ospC of GenBank accession number U08284 (SEQ ID NO:86).

Description

BACKGROUND OF THE INVENTION

Lyme disease begins at the site of a tick bite, producing a primary infection with spread of the organism to secondary sites occurring early in the course of infection. Lyme disease is a progressive multi-system disorder and is the most common vector-borne disease in both North America and Europe. This disease was first described as a focus of pediatric arthritis patients in Old Lyme, Conn. (Steere, A. C., et al., Arth. Rheum., 20:17 (1977)). The association of this syndrome with the bite of the deer tick, Ixodes scapularis, led to the identification of the spirochete Borrelia burgdorferi as the causative agent (Burgdorfer, W., et al. Science, 216:1317-1319 (1982)). As culture isolation of the bacterium from clinical and field samples became more efficient, Baranton and colleagues described three pathogenic genospecies, B. burgdorferi sensu stricto (B. burgdorferi or B.b.s.s.), B. afzelii, and B. garinii (Baraton, G., et al., Int. J. Syst. Bacteriol., 42:378-383 (1992)). These are members of a species complex, B. burgdorferi sensu lato, which consists of at least 10 different genospecies (Piken, R. N., et al., J. Invest. Dermatol., 110:211-214 (1998); Postic, D., et al., Int. J. Syst. Bacteriol., 44:743-752 (1994); Valsangiacomo, C. T., et al., Int. J. Syst. Bacteriol., 47:1-10 (1997)). B. burgdorferi, B. afzelii and B. garinii are thought to be pathogenic and all are found in Europe, but in North America, B. burgdorferi is the only pathogenic genospecies found. Each of these three genospecies is associated with distinct clinical manifestations (Van Dam, A. P. et al., Clin. Infect. Dis., 17:708-717 (1993)). This implies that differences in genospecies may play an important role in the wide array of clinical manifestations observed in Lyme Disease. However, because OspC is highly variable in its sequence, the protection is limited to the Borrelia burgdorferi strain expressing the same immunizing OspC encoded by a specific allele. Challenge with heterologous isolates, expressing other ospC alleles results in infections (Probert, W. S., et al., J. Infect. D., 175:400-405 (1997)). OspC is very diverse (Jauris-Heipke, S., et al., Med. Microbiol. Immunol. 182:37-50 (1993)). Livey et al. found thirty-four alleles in seventy-six B. burgdorferi sensu lato isolates (Livey, I., et al., Mol. Microbiol. 18:257-269 (1995)).

Currently, Lyme Disease is treated with antibiotics. However, such treatment is not always successful in clearing the infection. Treatment is often delayed due to improper diagnosis with the deleterious effect that the infection proceeds to a chronic condition, where treatment with antibiotics is often not useful. One of the factors contributing to delayed treatment is the lack of effective diagnostic tools. W

Furthermore, while antigens such as OspC are known to be protective, in some cases the existence of multiple alleles of these antigens greatly hinders the development of vaccines based on such antigens that would protect against more than one strain of Borrelia. Two independent trials of first generation vaccines for the prevention of Lyme disease, recently studied the efficacy and safety of a vaccine that is based on recombinant outer surface protein A (OspA) (Sigal, L. H. et al., N. Engl. J. Med 339:216-222, 1998; Steere, A. C. et al., N. Engl. J. Med. 339:209-215, (1998)). However, a vaccine that consists of recombinant OspA may require frequent booster immunizations. Natural infection with B. burgdorferi does not elicit an antibody response to OspA, as it does against OspC. What is needed is a selection of Borrelia antigens that can be used to either diagnose or vaccinate against all or most forms of Borrelia that cause systemic disease.

Differences in the frequency of B. burgdorferi, B. garinii, and B. afzelii in ticks and human infection has lead to the hypothesis that the different genospecies are differentially pathogenic (Picken, R. N. et al., J. Invest. Dermatol. 110:211-214, 1998; Van Dam, A. P. et al., Clin. Infect. Dis. 17:708-717, 1993). Nevertheless, the number of different strains within a given genospecies and the differences between the strains of a given genospecies as well as between genospecies impose obstacles in the development of immunogenic protein compounds for use as diagnostic and vaccine agents in the detection, prevention and treatment of Lyme disease. A number of investigators have used OspC as a serodiagnostic antigen for early Lyme disease (Fung, B. P. et al., Infect. Immun. 62:3213-3221, 1994; Gerber, M. A. et al., J. Infect. Dis. 171:724-727, 1995; Padula, S. J. et al., J. Clin. Microbiol. 32:1733-1738, (1994)). In these tests, the use of OspC as a diagnostic antigen gave highly specific, but not sensitive results. However, these studies included only one B. burgdorferi strain and therefore only one type of OspC. Routine tests for the diagnosis of Lyme disease also use a single strain protocol and therefore a single OspC allele for detection of antibody to the sprirochete. It is not clear what mixture of OspC proteins must be used to make useful diagnostic and vaccine tools, effective against more than one Lyme disease causing strains of Borrelia, if not against most if not all of the invasive strains within a genospecies.

Preferably, such a mixture would be effective against all invasive strains of Lyme disease causing Borrelia.

SUMMARY OF THE INVENTION

The present invention is drawn to a composition comprising OspC polypeptides from Lyme Disease causing Borrelia. In one embodiment, the composition of the present invention comprises an OspC polypeptide or fragment thereof from at least two Borrelia burgdorferi OspC families selected from the group consisting of A, B, I and K, excepting the combination consisting of two OspC proteins, wherein one OspC protein is from OspC family A and the second OspC protein is from OspC family I. In another embodiment, the composition of the present invention comprises at least one OspC polypeptide or fragment thereof from each of Borrelia afzelii OspC families A and B.

The present invention is also drawn to a method of immunizing an animal against Lyme disease, comprising administering a composition comprising OspC polypeptides from Lyme Disease causing Borrelia. In one embodiment of the present invention, the composition comprises a OspC polypeptide or fragment thereof from at least two Borrelia burgdorferi OspC families selected from the group consisting of: A, B, I and K, excepting the combination consisting of two OspC proteins, wherein one OspC protein is from OspC family A and the second OspC protein is from OspC family I. In another embodiment of the present invention, the composition comprises at least one OspC polypeptide or fragment thereof from each of Borrelia afzelii OspC families A and B. The composition of the present invention together with suitable excipients and/or adjuvants is administered to an animal such that the animal develops an immune response to at least one OspC polypeptide of the composition.

The present invention is also drawn to a method of detecting an immune response to Lyme Disease causing Borrelia in a host sample. The method comprises contacting a host sample with a composition comprising OspC polypeptides from Lyme disease causing strains of Borrelia, such that anti-OspC antibodies, if present, in said sample bind to said OspC polypeptides. In one embodiment, the composition comprises at least one OspC polypeptide or fragment thereof from each of Borrelia burgdorferi OspC families A, B, I and K. The amount of antibodies that have bound said OspC polypeptides or fragments thereof are measured; thereby detecting an immune response to Lyme disease causing Borrelia.

The present invention is also drawn to a diagnostic kit comprising OspC polypeptides from Lyme Disease causing Borrelia. In one embodiment of the present invention, the diagnostic kit comprises at least one OspC polypeptide or diagnostic fragment thereof from each of Borrelia burgdorferi OspC families A, B, I and K. In another embodiment of the present invention, the diagnostic composition comprises at least one OspC polypeptide or diagnostic fragment thereof from each of Borrelia afzelii OspC families A and B.

In other embodiments of the present invention, the composition comprises at least one OspC polypeptide or fragment thereof from each of Borrelia afzelii OspC families A and B. In still other embodiments, the composition comprises OspC polypeptides or fragments thereof from Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii and combinations thereof.

The present invention is also drawn to chimeric proteins for use in the methods of the present invention. In one embodiment, the present invention is drawn to a chimeric protein comprising OspC polypeptides from two or more OspC families of Lyme Disease causing Borrelia. In one embodiment, the families comprise Borrelia burgdorferi OspC families A, B, I and K. In other embodiment, the families comprise Borrelia afzelii OspC families A and B. In still other embodiments, the composition comprises chimeric OspC polypeptides or fragments thereof from Borrelia burgdorferi, Borrelia afzelii, Borrelia garinii and combinations thereof.

The chimeric proteins of the present invention comprise at least a first and a second polypeptide of OspC, such that the first polypeptide comprises OspC from about base 26 to about base 630 of a first ospC gene and the second polypeptide comprises about base 28 to about base 570 of a second ospC gene. The chimeric proteins of the present invention can be used in the immunization and detection methods of the present invention.

The present invention provides the minimum number of Borrelia burgdorferi and Borrelia afzelii families that are responsible for systemic disease in humans and is useful for vaccines and diagnostic kits. The present invention provides a combination of proteins that, when used as a vaccine, prevent Lyme disease from becoming systemic. The proteins and chimeric proteins of the present invention can be effective in preventing of Lyme disease as well as having a therapeutic effect on established infection, for example after the tick bite is noticed by the patient. The proteins and chimeric proteins of the present invention are expected to act at the level of the tick as well as the level of the host in preventing both infection and disease due to Borrelia burgdorferi, Borrelia afzelii and/or Borrelia garinii. The present invention allows the development of a worldwide vaccine comprising only six proteins necessary to generate a protective immune response against all pathogenic strains of Borrelia burgdorferi and Borrelia afzelii.

The present invention also provides improved diagnostic tools. Because of the present invention it is now possible to prepare diagnostic tools comprising OspC antigens representing the four pathogenic families of Borrelia burgdorferi and/or the two pathogenic families of Borrelia afzelii, thereby detecting clinically important exposure to pathogenic bacteria while overlooking the remainder of the families which do not cause pathogenic disease.

As demonstrated herein, a significant proportion if not all, systemic B. burgdorferi sensu stricto infections in humans are associated with four ospC groups and that a significant portion, if not all, systematic B. afzelii infections in humans are associated with two ospC groups. Vaccines against OspC are known to be protective, but have been limited by the diversity of ospC (Probert, W. S. et al., J. Infect. D. 175:400-405, (1997)). The polypeptides of tie present invention provide immunogenic proteins, fragments and chimeric proteins thereof for highly protective vaccines and diagnostics. The present invention provides a vaccine that includes one or more of these four forms of OspC. The vaccines of the present invention should be an important second level of protection against disseminated infection of the B. burgdorferi spirochete. Furthermore, single-stranded conformational polymorphism (SSCP) analysis described herein may provide a rapid and powerful tool to monitor vaccine efficacy by detecting rare or new invasive ospC groups.

New diagnostic assays of the present invention, based on major ospC groups A, B, I, and K are useful to identify those at risk for progressive illness. Given that OspC proteins are antigenically variable, individuals infected with one strain may produce an antibody response that is not reactive with an OspC protein from a different major group. Antibody detection using antigen preparations of the present invention, incorporating a proper mix of invasive clones of B. burgdorferi will be much more sensitive than the present, single strain protocols. The compositions of the present invention not only elicit humoral and cell mediated immune responses, the compositions of the present invention are also capable of detecting both humoral and cell mediated immune response when used to test a host sample.

The present invention provides both lipidated OspC polypeptides, fragments thereof and chimeric proteins comprising two or more OspC polypeptides, wherein the chimeric protein has a lipidation signal, such as the lipidation signal from outer surface protein B at the 5' terminus of the gene encoding the chimera. Furthermore, the present invention provides unlipidated OspC polypeptides, fragments thereof and chimeric proteins comprising two or more OspC polypeptides, wherein the gene encoding the chimeric protein does not comprise a lipidation signal and the chimeric protein is not lipidated. Unlipidated OspC polypeptides, fragments thereof and chimeric proteins thereof are advantageous due to simpler production methods, improved yields of protein and simpler purification. The unlipidated chimeric proteins of the present invention unexpectedly elicit an immune response against Lyme disease causing strains of Borrelia at least as broadly reactive as lipidated OspC proteins that are used as a positive control. Furthermore, the unlipidated OspC chimeric proteins of the present invention elicit an immune response to more than one genospecies of Lyme disease causing strains of Borrelia, including genospecies and strains that are not used to generate the chimeric OspC immunogen.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of the frequency distribution of major ospC groups among B. burgdorferi isolates from Eastern Long Island Ixodes scapularis ticks.

FIG. 2 is a bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or recombinant chimeric Borrelia protein (X-axis) against the indicated OspC antigens (legend) where the serum is from the first bleed.

FIG. 3 is a bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or recombinant chimeric Borrelia protein (X-axis) against the indicated OspC antigens (legend) where the serum is from the second bleed.

FIG. 4 is a bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or chimeric recombinant Borrelia protein (X-axis) against the indicated strains of Borrelia burgdorferi sensu stricto (legend).

FIG. 5 is a bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or chimeric recombinant Borrelia protein (X-axis) against the indicated strains of Borrelia burgdorferi sensu lato (legend).

FIG. 6 is bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or chimeric recombinant Borrelia protein (X-axis) against the indicated strains of Borrelia afzelii (legend).

FIG. 7 is bar graph showing the reactivity of serum from mice immunized with the indicated Borrelia protein or chimeric recombinant Borrelia protein (X-axis) against the indicated strains of Borrelia garinii (legend).

FIG. 8 is a Table comparing the reactivity of lipidated OspC proteins C1 and C2 against sera from patients with the indicated condition with the reactivity of the unlipidated chimeric proteins of the present invention, where the number in parentheses is the total number of sera tested in that category.

DETAILED DESCRIPTION OF THE INVENTION

As described herein, initially nineteen groups of ospC from B. burgdorferi sensu stricto were found within a small tick population (Wang, I-N., et al., Genetics, 151:15-30 (1999)). Major ospC groups were defined using the observation that ospC alleles are either very similar, having less than 2% sequence divergence, or very different, having greater than 8% sequence divergence, with most having greater than 14% sequence divergence.

Based on sequence divergences, alleles of ospC can be grouped into twenty-one major groups (Table II). To assess whether strain differences as defined by a given ospC group are linked to invasiveness and pathogenicity, the frequency distributions of major ospC groups from ticks, from the primary erythema migrans (EM) skin lesion, and from secondary sites, principally from blood and spinal fluid, were compared. As described herein, the frequency distribution of ospC groups from ticks is significantly different from that of primary site infection which in turn is significantly different from secondary sites. The major ospC groups A, B, I and K increased in frequency from ticks to the primary site and were the only groups found in secondary sites of the infection. Therefore, three categories of major ospC croups are defined herein. One category is common in ticks but very rarely, if ever, causes human disease, a second category that causes only local infection at the tick bite site, and a third category that causes systemic or disseminated disease. While many ospC groups found in ticks were also found in primary skin lesions, the frequency distributions are significantly different between ticks and primary skin lesions (Table III). All ospC groups were found more or less commonly in ticks. However, only four groups are commonly found in skin lesions or secondary infections (Tables III and IV). As described herein, the primary skin lesions harbored Borrelia having ospC groups other than A, B, I or K rarely or not at all. More importantly, only these four ospC groups were found in secondary sites. The finding that all systemic B. burgdorferi sensu stricto infections are associated with four ospC groups has importance in the diagnosis, treatment and prevention of Lyme disease.

There is evidence that ospC has been transferred between strains and even between genospecies (Wang I-N. et al., Genetics, 151:15-30 (1998)). This is not true of Borrelia chromosomal genes (Dykhuizen, D. E., et al., Proc. Natl. Acad. Sci., 30:10163-10167 (1999); Maynard Smith, J. and Smith, N. H., Mol. Biol. Evol., 15:590-599 (1998)). However, ospA and ospC alleles in B. burgdorferi sensu stricto are almost completely linked (Wang I-N. et al., Genetics, 151:15-30 (1999)). This suggests that once an ospC allele has been transferred into a particular background, there is little or no selection for another similar recombination event. Thus, each major ospC group represents a clonal population descended from a single recombination.

Twenty percent of untreated erythema migrans clear spontaneously without causing any systemic complications (Steere, A. C. et al., Arth. Rheum. 20:7-17, (1977)). As demonstrated herein, this is not significantly different (p=0.25 for a 2 by 2 contingency test with double dichotomy) from the percent of non-invasive strains found in the skin, suggesting that the erythema migrans that clear spontaneously are caused by non-invasive clones.

There is extensive genetic and antigenic diversity of ospC in all three pathogenic genospecies of B. burgdorferi sensu lato (Livey, I. et al., Mol. Microbiol. 18:257-269, 1995; Masuzawa, T. et al., Clin. Diagn. Lab. Immunol. 4:60-63, 1997; Picken, R. N. et al., J. Invest. Dermatol. 110:211-214, 1998; Theisen, M. et at., J. Clin. Microbiol. 31:2570-2576, 1993; Wang, I-N. et al., Genetics 151:15-30 (1999). As demonstrated herein, only four groups of ospC alleles are linked to both infectivity and invasiveness, and that invasiveness is confined to a small number of ospC clones. It is clear that the ospA and ospC alleles are tightly linked even though they are on different plasmids (Wang, I-N. et at., Genetics 151:15-30 (1999)). If the invasiveness is caused by allelic variation at another locus, this variation is likely to be tightly linked to the ospC variation. Thus, ospC is a good marker for human pathogenicity and perhaps its determinator. These findings have important implications not only for our understanding of the pathogenesis of this disease but for its diagnosis and prevention.

Spirochetemia is a transient phenomenon, but is presumably key in seeding secondary skin sites, the heart, joints, and nervous system, where these Borrelia cause the secondary and tertiary clinical manifestations of Lyme disease. All four invasive groups of Borrelia burgdorferi were found in isolates from blood and CSF. The one joint isolate belonged to group A. However, it can be inferred that groups not found in the blood will not be found in the joints since most if not all dissemination of Borrelia to secondary sites is via blood.

Normally, model organisms are used as substitutes for experiments on humans. However, this substitution works only as long as the properties of the model organism and of humans are the same for the studied phenomena. The human immune system plays a critical role which is expected to be different from the immune response in model organisms, particularly the mouse. Humans are accidental and usually dead-end hosts while the mouse is a critical host reservoir. The field of population genetics has developed sound procedures for reaching conclusions from survey data.

The chimeric polypeptides of the present invention elicit specific immune responses to OspC. The chimeric polypeptides also elicit immune response against strains of Lyme disease causing Borrelia of the same genospecies as that represented by the chimeric OspC as well as Lyme disease causing Borrelia of different genospecies than that represented by the chimeric OspC. The immune response includes humoral responses, secretory responses, cell-mediated responses and combinations thereof in an animal treated with the compositions of the present invention. The compositions of the present invention can include additional components suitable for in vitro and in vitro use. These additional components include buffers, carrier proteins, adjuvants, preservatives and combinations thereof.

The immunogenic compositions of the present invention can be used to immunize animals including humans. Immunization is understood to elicit specific immunogenic responses as described above. As described herein, an immunogenic response includes responses that result in at least some level of immunity in the treated animal, where the animal was treated with a composition comprising at least one protein or chimeric protein of the present invention. In one embodiment, the treated animal develops immunity against infection by Lyme disease causing Borrelia, wherein the chimeric proteins of the present invention elicit responses against Borrelia burgdorferi, Borrelia afzelii and Borrelia garinii.

Immunity, as described herein, is understood to mean the ability of the treated animal to resist infection, to resist systemic infection, to overcome infection such as systemic infection or to overcome infection such as systemic infection more easily or more quickly when compared to non-immunized or non-treated individuals. Immunity can also include an improved ability of the treated individual to sustain an infection with reduced or no clinical symptoms of systemic infection. The individual may be treated with the chimeric proteins of the present invention either proactively, e.g. once a year or maybe treated after sustaining a tick bite.

For use as a vaccine, the composition of the present invention can include suitable adjuvants, well known in the art, to enhance immunogenicity, potency or half-life of the chimeric proteins in the treated animal. Adjuvants and their use are well known in the art (see for example PCT Publication WO 96/40290, the entire teachings of which are incorporated herein by reference). The composition can be prepared by known methods of preparing vaccines. For example, the OspC proteins or chimeric proteins to be used in the compositions can be isolated and/or purified by known techniques such as by size exclusion chromatography, affinity chromatography, preparative electrophoresis, selective precipation or combinations thereof. The prepared proteins or chimeric proteins can be mixed with suitable other reagents as described above, where the chimeric protein is at a suitable concentration. The dosage of protein or chimeric protein will vary from one .mu.g to 500 .mu.g and depends upon the age, weight and/or physical condition of the animal to be treated. The optimal dosage can be determined by routine optimization techniques, using suitable animal models.

The composition to be used as a vaccine can be administered by any suitable technique. In one embodiment, administration is by injection, e.g. subcutaneous, intramuscular, intravenous, or intra peritoneal injection. In another embodiment, the composition is administered to mucosa, e.g. by exposing nasal mucosa to nose drops containing the proteins of chimeric proteins of the present invention. In another embodiment, the immunogenic composition is administered by oral administration. In another embodiment of the present invention the chimeric proteins are administered by DNA immunization.

Like many outer surface proteins of Borrelia, OspC is produced in the Borrelia spirochete with 5' lipidation. The chimeric polypeptides of the present invention can be produced in both lipidated and non-lipidated form. In one embodiment, the lipidation signal encoded by the wild type ospC is removed from the coding sequence, such that the gene or chimeric gene encodes a non-lipidated OspC or chimeric OspC polypeptide. In another embodiment of the present invention, the lipidation signal of the wild type ospC gene is replaced with the lipidation signal of the ospB gene. In this embodiment, a lipidated OspC or OspC chimeric protein is produced.

The polypeptides of the present invention can be recombinantly expressed in suitable microbial hosts, wherein said hosts include, but are not limited to, bacterial hosts, such as E. coli, fungal hosts S. cerevisiae, or cell culture hosts such as mammalian cell culture or insect cell culture.

While the lack of lipidation signal allows for the production of large amounts of OspC proteins and chimeric OspC proteins, the tack of lipidation signal was previously thought to render outer surface proteins of Borrelia less or non-immunogenic. However, as described herein, the non lipidated chimeric polypeptides of the present invention unexpectedly elicit as broad an immunogenicity as lipidated OspC protein (FIGS. 2 and 3) and greater immunogenicity against strains of other genospecies (FIG. 5-7) compared to the positive controls, which were lipidated OspC from B31 and lipidated OspC from C12.

The proteins and chimeric proteins of the present invention are also antigenic and therefore useful to detect or diagnose the presence of Lyme disease causing Borrelia, especially Borrelia from groups capable of causing disseminated symptoms of Lyme disease. As described herein, disseminated symptoms refers to infection outside of the erythema migrans skin lesion, e.g. infection in blood, CNS or synovia. As described herein, antigenic refers to the ability of a compound to bind products of an immune response, such as antibodies, T-cell receptors or both. Such responses can be measured using standard antibody detection assays, such as ELISA or standard T-cell activation assays.

The present invention is drawn to compositions comprising OspC polypeptides from Lyme disease causing Borrelia and chimeric OspC polypeptides. In one embodiment of the present invention, compositions include one or more OspC polypeptide or fragment thereof from at least two Borrelia burgdorferi ospC groups, referred also herein as families, selected from the group consisting of A, B, I and K, excepting the combination consisting of two OspC polypeptides from the A and I families. In another embodiment of the present invention, the compositions of the present invention include at least one OspC polypeptide or fragment thereof from each of Borrelia burgdorferi ospC families A, B, I and K. In another embodiment, the composition includes at least one OspC polypeptide or fragment thereof from each of Borrelia afzelii OspC families A and B. In still another embodiment, the composition includes OspC polypeptides from at least one Borrelia burgdorferi OspC group or family member selected from the group consisting of A, B, I and K and at least one Borrelia afzelii OspC family member selected from the group consisting of A and B.

As described herein, the ospC families of the present invention share about 98% homology at the nucleic acid level between strains of the same family and share no more than about 92% homology at the nucleic acid level between strains of different families. Determination of homology, excludes any non-ospC sequences. Members of the same ospC family have similar antigenic profiles, e.g. elicit immune response against similar strains of Lyme disease causing Borrelia. The chimeric proteins of the present invention unexpectedly elicit immune response to Lyme disease causing Borrelia of different genospecies than the genospecies from which the component polypeptides were derived. In one embodiment of the present invention, Borrelia burgdorferi ospC family A comprises strains B31, CA4, HII, IPI, IP2, IP3, L5, PIF, PKA, TXGW and strains of Borrelia containing ospC allele OC1. In another embodiment of the present invention, Borrelia burgdorferi ospC family B comprises strains 35B808, 61BV3, BUR, DK7, PB3, ZS7 and strains containing ospC alleles OC2 and OC3. In still another embodiment of the present invention, Borrelia burgdorferi ospC family I comprises strains 297, HB19 and strains containing ospC allele OC10, wherein strain 297 is characterized by ospC of GenBank Accession No. L42893 (SEQ ID NO:85). In still another embodiment of the present invention, Borrelia burgdorferi ospC family K comprises strains 272, 297, 28354, KIPP, MUL and strains containing ospC allele OC12 and OC13, wherein strain 297 is characterized by ospC of GenBank Accession No. U08284 (SEQ ID NO:86).

In another embodiment of the present invention, said compositions comprise an OspC polypeptide or fragment thereof from each of Borrelia afzelii OspC families A and B. In one embodiment of the present invention, Borrelia afzelii OspC family A comprises strains Pbo, Pwud, Pko, Pgau, DK2, DK3, DK21, DK8, Bfox and JSB. In another embodiment of the present invention Borrelia afzelii OspC family B comprises strains DK5, ACA1, DK9, XB18h, Ple and 143M. As described above for Borrelia burgdorferi the compositions also include chimeric OspC polypeptides of Borrelia afzelii families A and B.

In one embodiment of the present invention, the OspC polypeptide OspC polypeptide is a chimeric OspC comprising at least one OspC protein variable region or portion thereof from at least one ospC gene. In one embodiment of the present invention, the OspC polypeptide variable region is encoded by a nucleic acid comprising the 3' two thirds of the OspC gene, about nucleotide 150 to about nucleotide 519 of an ospC gene (or about codon 50 to about codon 173). In another embodiment of the present invention, said OspC polypeptide variable region is encoded by a nucleic acid wherein the nucleic acid comprises, for example, nucleotide 244 to about nucleotide 519 (or about codon 81 to about codon 173), nucleic acid from about nucleotide 337 to about nucleotide 519 (or about codon 112 to about codon 173), nucleic acid from about nucleotide 418 to about nucleotide 519 (or about codon 139 to about codon 173), nucleic acid from about nucleotide 244 to about nucleotide 418 (or about codon 81 to about codon 139), nucleic acid from about nucleotide 337 to about nucleotide 418 (or about codon 112 to about codon 139), and nucleic acid from about nucleotide 150 to about nucleotide 243 (or about codon 50 to about codon 81) of an ospC gene.

In still another embodiment, the chimeric OspC polypeptides of the present invention comprises two or more polypeptides wherein a first polypeptide is from a first ospC gene from about nucleotide 26 (or about codon 8) to about nucleotide 630 (or about codon 210). In another embodiment, the first polypeptide is from about nucleotide 28. In another embodiment, the first polypeptide is from about nucleotide 53. In still another embodiment, the first polypeptide is from about nucleotide 55. In another embodiment, the first polypeptide is up to about nucleotide 621 of a first ospC gene. In still another embodiment, the first polypeptide is up to about nucleotide 582 of a first ospC gene. In still another embodiment, the first poly peptide is up to about nucleotide 576 of a first ospC gene.

The chimeric OspC of the present invention further comprises a second polypeptide, wherein the second polypeptide is derived from a second ospC gene from about nucleotide 28 (or about codon 9) to about nucleotide 571 (or about codon 190).

It is understood that the polypeptides than comprise the chimeric polypeptide can include extra nucleotides or fewer nucleotides from the given ospC gene from which the polypeptide is derived in order to simplify the construction of the gene encoding the chimeric polypeptide, e.g. to allow for the use of convenient restriction endonuclease sites or to allow the ligation of the gene fragments such that a contiguous coding region is created. Based on the guidance provided herein, one of ordinary skill in the art would readily be able to add or remove nucleotides from the termini of the gene fragments encoding the polypeptides of the chimeric OspC protein to generate chimeric proteins of the present invention with no or only routine experimentation. Furthermore, there can be an extra about 1 to about 10 amino acids on the N- and/or C-terminus of the polypeptides and chimeric proteins of the present invention and still retain the properties of the present invention.

The present invention also includes variants or altered versions of the OspC polypeptides and nucleic acids encoding said polypeptides. As used herein, a variant of a polynucleotide or polypeptide refers to a molecule that is substantially similar to either the entire molecule, or a fragment thereof. For example, when the molecule is a polypeptide, variant refers to an amino acid sequence that is altered by one or more amino acids, wherein either a biological function, structure or antigenicity of said sequence or combination thereof is maintained in the variant. The variant may have "conservative" changes, wherein a substituted amino acid has similar structural or chemical properties, e.g., replacement of leucine with isoleucine. Or a variant may have "nonconservative" changes, e.g., replacement of a glycine with a tryptophan. Similar minor variations may also include amino acid deletions or insertions, or both. Similarly. when the molecule is a polynucleotide, variant refers to a sequence that is altered by one or more nucleotides. The variant may have silent variations, wherein the change does not alter the amino acid encoded by the triplet comprising said variation or the variation is not silent, that is, alterations in encoded amino acids are generated.

As used herein, the term "altered version" refers to a polynucleotide sequence or a polypeptide sequence, wherein said sequence has one or more differences with a native or wildtype version of said sequence.

In another embodiment, the invention includes an isolated nucleic acid molecule comprising a nucleotide sequence which is homologous to one or more of the chimeric sequences of the present invention, or complements thereof. Such a nucleotide sequence exhibits at least about 80% homology, or sequence identify, with one of the chimeric OspC sequences, such that the encoded protein retains the antigenicity and immunogenicity of the unaltered chimeric protein. Preferably, the homologous sequences of the present invention shares at least about 90% homology or sequence identity with the corresponding unaltered chimeric ospC. Particularly preferred sequences have at least about 95% homology or have essentially the same sequence.

The altered nucleic acids and homologous nucleic acids of the present invention hybridize to the corresponding chimeric ospC under conditions of high stringency. A general description of stringency for hybridization conditions is provided by Ausubel, F. M., et al., Current Protocols in Molecular Biology, Greene Publishing Assoc. and Wiley-Interscience 1987, & Supp. 49, 2000. Factors such as probe length, base composition, percent mismatch between the hybridizing sequences, temperature and ionic strength influence the stability of nucleic acid hybrids. Thus, stringency conditions, sufficient to allow hybridization of oligonucleotides to the template, can be varied by routine optimization to generate high stringency conditions.

Alternatively, conditions for stringency are as described in WO 98/40404, the teachings of which are incorporated herein by reference. In particular, examples of highly stringent, stringent, reduced and least stringent conditions are provided in WO 98/40404 in the Table on page 36. Examples of stringency conditions are shown in Table I below which is from WO98/40404 to Jacobs et al.,: highly stringent conditions are those that are at least as stringent as, for example, conditions A-F; stringent conditions are at least as stringent as, for example. conditions G-L; and reduced stringency conditions are at least as stringent as, for example, conditions M-R.

TABLE-US-00001 TABLE 1 Hybrid Wash Stringency Polynucleotide Length Hybridization Temperature and Temperature Condition Hybrid (bp).sup..dagger-dbl. Buffer.sup..dagger. and Buffer.sup..dagger. A DNA:DNA .gtoreq.50 65.degree. C.; 1xSSC -or- 65.degree. C.; 0.3xSSC 42.degree. C.; 1xSSC, 50% formamide B DNA:DNA <50 T.sub.B*; 1xSSC T.sub.B*; 1xSSC C DNA:RNA .gtoreq.50 67.degree. C.; 1xSSC -or- 67.degree. C.; 0.3xSSC 45.degree. C.; 1xSSC, 50% formamide D DNA:RNA <50 T.sub.D*; 1xSSC T.sub.D*; 1xSSC E RNA:RNA .gtoreq.50 70.degree. C.; 1xSSC -or- 70.degree. C.; 0.3xSSC 50.degree. C.; 1xSSC, 50% formaimde F RNA:RNA <50 T.sub.F*; 1xSSC T.sub.F*; 1xSSC G DNA:DNA .gtoreq.50 65.degree. C.; 4xSSC -or- 65.degree. C.; 1xSSC 42.degree. C.; 4xSSC, 50% formamide H DNA:DNA <50 T.sub.H*; 4xSSC T.sub.H*; 4xSSC I DNA:RNA .gtoreq.50 67.degree. C.; 4xSSC -or- 67.degree. C.; 1xSSC 45.degree. C.; 4xSSC, 50% formamide J DNA:RNA <50 T.sub.J*; 4xSSC T.sub.J*; 4xSSC K RNA:RNA .gtoreq.50 70.degree. C.; 4xSSC -or- 67.degree. C.; 1xSSC 50.degree. C.; 4xSSC, 50% formamide L RNA:RNA <50 T.sub.L*; 2xSSC T.sub.L*; 2xSSC M DNA:DNA .gtoreq.50 50.degree. C.; 4xSSC -or- 50.degree. C.; 2xSSC 40.degree. C.; 6xSSC, 50% formamide N DNA:DNA <50 T.sub.N*; 6xSSC T.sub.N*; 6xSSC O DNA:RNA .gtoreq.50 55.degree. C.; 4xSSC -or- 55.degree. C.; 2xSSC 42.degree. C.; 6xSSC, 50% formamide P DNA:RNA <50 T.sub.P*; 6xSSC T.sub.P*; 6xSSC Q RNA:RNA .gtoreq.50 60.degree. C.; 4xSSC -or- 60.degree. C.; 2xSSC 45.degree. C.; 6xSSC, 50% formamide R RNA:RNA <50 T.sub.R*; 4xSSC T.sub.R*; 4xSSC

.dagger-dbl.: The hybrid length is that anticipated for the hybridized region(s) of the hybridizing polynucleotides. When hybridizing a polynucleotide to a target polynucleotide of unknown sequence, the hybrid length is assumed to be that of the hybridizing polynucleotide. When polynucleotides of known sequence are hybridized, the hybrid length can be determined by aligning the sequences of the polynucleotides and identifying the region or regions of optimal sequence complementarity. .dagger.: SSPE (1.times.SSPE is 0.15M NaCl, 10 mM NaH.sub.2PO.sub.4, and 1.25 mM EDTA, pH 7.4) can be substituted for SSC (1.times.SSC is 0.15M NaCl and 15 mM sodium citrate) in the hybridization and wash buffers; washes are performed for 15 minutes after hybridization is complete. *T.sub.B-T.sub.R: The hybridization temperature for hybrids anticipated to be less than 50 base pairs in length should be 5-10.degree. C. less than the melting temperature (T.sub.m) of the hybrid, where T.sub.m is determined according to the following equations. For hybrids less than 18 base pairs in length, T.sub.m(.degree. C.)=2(# of A+T bases)-4(# of G+C bases). For hybrids between 18 and 49 base pairs in length, T.sub.m(.degree. C.)=81.5+16.6(log.sub.10[Na.sup.+])+0.41(%G+C)-(600/N), where N is the number of bases in the hybrid, and [Na.sup.+] is the concentration of sodium ions in the hybridization buffer ([Na.sup.+] for 1.times.SSC=0.165 M).

As used herein, "isolated" refers to nucleic acid or polypeptide that has been removed from its original environment (e.g., the natural environment if it is naturally occurring). For example, polynucleotide or DNA or polypeptide, which is separated from some or all of the coexisting materials in the natural system. An isolated polynucleotide can be part of a vector and/or composition, and still be isolated in that the vector or composition is not part of its natural environment. Likewise polypeptides can be part of a composition and still be isolated in that the composition is not part of its natural environment.

The chimeric proteins of the present invention comprise OspC proteins or polypeptides as described above from two or more OspC families of Lyme disease causing Borrelia as described in Table II. In one embodiment of the present invention, said families comprise Borrelia burgdorferi OspC families A, B, I and K and Borrelia afzelii OspC families A and B. The chimeric proteins of the present invention comprise, for example, a first OspC polypeptide encoded by a nucleic acid comprising a sequence from about codon 18 to about codon 210 of a first ospC gene. In another embodiment, the sequence is from about codon 8. In another embodiment, the sequence is to about codon 207. In another embodiment, the sequence is to about codon 194. In still another embodiment, the sequence is to about codon 192. The chimeric proteins of the present invention further comprise, for example, a second OspC polypeptide comprising an OspC variable polypeptide encoded by nucleic acid fragments as described above. In another embodiment of the present invention, the chimeric protein comprises two or more OspC variable polypeptides as described above.

The chimeric proteins of the present invention further comprise, for example, a second OspC polypeptide encoded by a nucleic acid comprising a sequence from about codon 9 to about codon 190 of a second ospC gene.

For the chimeric proteins of the present invention, at least two of said OspC polypeptides or immunogenic fragments thereof are fused together in a single protein, a chimeric protein, encoded by a single nucleic acid, wherein no two adjacent polypeptides in said fusion protein are found in the same configuration in a naturally occurring OspC protein.

In still another embodiment, the OspC proteins or chimeric proteins of the present invention from Borrelia burgdorferi and Borrelia afzelii are combined in a composition.

The present invention is drawn to a method of detecting an immune response to Lyme Disease causing Borrelia in a host sample. The method comprises contacting the host sample with a composition comprising OspC polypeptides from Lyme disease causing strains of Borrelia, such that anti-OspC antibodies, if present, in said sample bind to said OspC polypeptides. In one embodiment, the composition comprises one or more OspC polypeptide or diagnostic fragment thereof from two Borrelia burgdorferi OspC families selected from the group consisting of A, B, I and K, excluding the composition consisting of two OspC proteins wherein one OspC protein is from OspC family A and the second OspC protein is from OspC family I. The antibodies that bind the OspC polypeptides of the composition are detected or measured; thereby detecting an immune response to Lyme disease causing Borrelia. In another embodiment, the composition comprises at least two Borrelia OspC polypeptides or diagnostic fragment thereof from two Borrelia afzelii OspC families selected from the group consisting of A and B. In still another embodiment, the composition comprises polypeptides from OspC from Borrelia burgdorferi and Borrelia afzelii. In still another embodiment, the composition comprises one or more polypeptides from each of Borrelia burgdorferi families A, B, I and K and Borrelia afzelii families A and B. The composition can also comprise one or more of the chimeric polypeptides of the present invention.

The present invention is also drawn to kits comprising one or more OspC polypeptides or OspC chimeric polypeptides or combinations thereof together with suitable buffers and antibody detection reagents for the detection or diagnosis of Lyme disease causing strain of Borrelia. In another embodiment, the kits comprise nucleic acid sufficiently homologous to the OspC polypeptides or OspC chimeric polypeptides to detect nucleic acid encoding ospC genes from Lyme disease causing strains of Borrelia together with reagents to detect positive hybridization to target DNA or reagents to specifically DNA, for example.

For the purposes of a detection kit, "homologous" refers to two or more sequences that share substantial similarity but are not identical. Two DNA sequences are "substantially similar" when at least about 95% (preferably at least about 98%) of the nucleotides match over a defined length of the DNA sequences. Sequences that are substantially homologous can be identified by comparing the sequences using standard software available in sequence data banks, or in a Southern hybridization experiment under, for example, stringent conditions as defined for that particular system. Defining appropriate hybridization conditions is within the skill of the art. See. e.g., Ausubel et al., Current Protocols in Molecular Biology, John Wiley & Sons, Inc., New York; Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press. For purposes of the present invention, amino acid sequences having, for example, greater than 90 percent similarity are considered substantially homologous.

The vaccine compositions of the present invention elicit humoral and cell mediated immune responses in a host. Furthermore, the diagnostic compositions of the present invention are capable of detecting both humoral and cell mediated immune response from a host sample using standard immunodiagnostic techniques.

EXEMPLIFICATION

Example 1

Techniques

Borrelia Strains

One hundred and forty B. burgdorferi strains were isolated from primary erythema migrans (EM) lesions, blood or cerebrospinal fluid (CSF) of patients seen at the Lyme Disease Center at Stony Brook, N.Y., Lyme Disease Diagnostic Center at New York Medical College, Valhalla, N.Y. or the private practices of the two collaborating physicians on the eastern end of Long Island or were obtained from the Centers for Disease Control (CDC). All patients met the Centers for Disease Control surveillance definition for Lyme Disease (CDC, Morb. Mortal. Wkly. Rep 46:20-21, (1997)). Isolates from skin, blood and CSF were obtained using standard techniques (Barbour, A. G., Yale J. Biol. Med. 57:521-525, 1984; Berger, B. W. et al., J. Clin. Microbiol. 30:359-361, 1992; Wormser, G. P. et al., J. Clin. Microbiol. 36:296-298, (1998)). Punch biopsies were taken from the advancing border of the erythema migrans lesion and incubated in BSK-H medium (Sigma, St. Louis, Mo.) at 34.degree. C. to create a culture. There was little culture bias as determined by direct analysis of biopsy tissue compared to culture isolates (Seinost, G. et al., Arch. Derm., 135:1329-1333, (1999)), unlike isolation of B. burgdorferi from unfed ticks (Norris, D. E. et al., J. Clin. Microbiol. 35:2359-2364, (1997)). In addition, twenty-two B. burgdorferi sensu stricto ospC sequences were retrieved from GenBank. The tick data used was either from GenBank or from the study of Wang et al. (Wang, I-N. et al., Genetics 151:15-30 (1999)).

DNA Isolation

For isolation of genomic Borrelia DNA, log phase cells were harvested by centrifugation at 10,000 RPM for 30 minutes at 4.degree. C. The bacterial pellet was resuspended in Tris/saline-buffer (10 mM Tris (pH 7.5), 150 mM NaCl). The bacteria were then pelleted and resuspended in TNE (10 mM Tris (pH 7.5) 150 mM NaCl, 1 mM EDTA). Freshly prepared lysozyme (20 mg/ml in TNE), sodium dodecyl sulfate (10%) and proteinase K (20 mg/ml) were added and the mixture was incubated at 50.degree. C. for one hour, followed by RNAse treatment. DNA was extracted with phenol/chloroform, precipitated with ethanol and resuspended in TE buffer.

Polymerase Chain Reaction

The ospC gene was amplified using PCR, as described previously (Wang, I-N. et al., Genetics 151:15-30 (1999)). The OspC gene was amplified using two external primers: 5'-AAA GAA TAC ATT AAG TGC GAT ATT-3' (+). SEQ ID NO: 1, beginning at base 6; and 5'-GGG CTT GTA AGC TCT TTA ACT G-3' (-), SEQ ID NO: 4, ending at base 602. The 5' half of ospC was amplified using SEQ ID NO: 1 and the reverse primer, 5'-CAA TCC ACT TAA TTT TTG TGT TAT TAG-3' (-) SEQ ID NO: 2; ending at base 345. The 3' half of ospC was amplified using the primer, 5'-TTG TTA GCA GGA GCT TAT GCA ATA TC-3' (+), SEQ ID NO: 3, beginning at base 289, and SEQ ID NO: 4 as the reverse primer. The external primers amplified a 597 bp fragment. Amplification of the 5' half produced a 340 bp fragment while amplification of the 3' half produced a 314 bp fragment. All the base numbers and amplified fragment sizes are based on ospC sequence of strain B31 (GenBank accession number U01894), with start codon as base 1.

Amplification was conducted in 50 .mu.l of a solution containing Perkin-Elmer Cetus 10.times. PCR buffer (100 mM Tris-HCl (pH 8.3), 500 mM KCl), 2.5 mM MgCl.sub.2, deoxynucleoside triphosphates at 0.2 mM per nucleotide, 2.5 U of Taq polymerase (Perkin-Elmer/Cetus) and 0.5 .mu.M of each primer. The amplification reaction was carried out for forty cycles in a DNA thermal-cycler (PTC-100; MJ Research, Inc., Watertown, Mass.) with an amplification profile of: denaturation at 95.degree. C. for 40 seconds, annealing at 54.degree. C. for 35 seconds, and extension at 72.degree. C. for 1 min. after an initial denaturation step at 96.degree. C. for 2 min. Negative controls were included in each experiment to control for contamination.

Cold SSCP-analysis.

SSCP analysis was chosen to characterize genetic variation of the isolated ospC gene fragments based on its exquisitely high detection rate of DNA polymorphisms and point mutations at a variety of positions in DNA fragments (Orita, M. et al., Proc. Natl. Acad. Sci. 862766-2770, (1989)). Single point mutations have been detected in fragments up to 800 bp long (Michaud, J. et al., Genomics, 13:389-394, (1992)). However, there is evidence that the ability of SSCP analysis to detect mutations begins to decline significantly as PCR fragments approach 400 bp in size (Hayashi, K., PCR Methods & Applications 1:34-38, (1991)). Therefore, in order to achieve high efficiency of detection of nucleotide polymorphism, the length of the PCR products used herein was 340 bp from the 5' half and 314 bp from the 3' half of ospC.

Amplified ospC gene fragments from all one hundred and forty strains were analyzed for genetic variations by the cold SSCP protocol described by Hongyo et al. (Hongyo, T. et al., Nucleic Acids Res. 21:3637-3642, (1993)). Briefly, 5 to 15 .mu.l of the PCR product was added to a mixture containing 4 .mu.l 5.times. TBE Ficoll sample Buffer (NOVEX, San Diego, Calif.) and 0.4 .mu.l 1 .mu.M methylmercury hydroxide (Alfa Aesaer, Ward Hill, Mass.). The amount of the PCR product used for the SSCP analysis was estimated after visualizing the PCR product on an agarose gel with ethidium bromide. The sample mixture was heated to 95.degree. C. for 4 min, then chilled on ice prior to loading the entire 20 .mu.l into the gel sample well. The sharpest bands were observed when the sample was applied to a pre-cast 20% TBE gel (NOVEX) electrophoresis system (ThermoFlow ETC Unit, NOVEX) with 1.25.times. TBE running buffer. Electrophoresis of SSCP products was conducted at a constant temperature of 8.degree. C. for 17 h at 240 volts in order to reveal discernable mobility shifts. Gels were stained with 0.5 .mu.l/ml ethidium bromide in 1.times. TBE buffer for 25 min and destained in distilled water for 30 min. Stained bands were viewed using a 340 nm UV staining box. Samples that showed more than two SSCP bands were reamplified to determine whether the bands found were real alleles or the product of PCR artifacts. Side-by-side SSCP analysis was performed in order to detect even slight shifts in electrophoretic mobility.

DNA Sequencing

The ospC gene or representatives of each mobility class were reamplified. Double-stranded PCR fragments were purified by agarose gel electrophoresis and subjected to automated DNA sequencing using fluorescent dideoxy terminator chemistry and the forward and reverse primers originally used for PCR amplification.

Statistical Analysis

Chi square analysis of contingency tables was performed. This analysis tests for significant difference in frequency distributions. The tables were 2.times.N where N is the number of major ospC groups distinguished. The average expected number in each element of the table needs to be about six or greater for an unbiased test (Zar, J. H., Biostatistical Analysis, 3rd ed, p. 206, (1996)). This means that the number of observations should be greater than 6 times 2N. When the expected average number was less than six, the major ospC groups with the lowest number in the sample were combined until the number of observations were about equal to or greater than 12N.

RESULTS

ospC Mobility Classes in Human B. burgdorferi Isolates.

One hundred and thirty-two isolates of B. burgdorferi sensu stricto from patient samples of skin, blood, and CSF (Table II) were propagated in vitro and used as a source of DNA for analysis. The ospC genotype of each strain was determined by cold SSCP analysis of the 5' end (340 bp) of the gene and was confirmed by SSCP analysis of the 3' end (314 bp) of ospC. In all B. burgdorferi isolates, the genetic variation at the 5' end of the gene corresponded to the variation at the 3' end. At least two representatives of each SSCP mobility class were subsequently sequenced. The sequences of the same mobility classes were identical in all samples and each mobility class had a unique sequence. Therefore, the sensitivity and specificity of SSCP analysis was 100%. Each SSCP mobility class was designated as an allele. Wang et al, recently described 13 ospC alleles (Wang, I-N. et al., Genetics 151:15-30). An additional five ospC (OC) mobility classes, OC14-18 are described herein. OC14 has the same ospC sequence as the ospC in strain 2591.

TABLE-US-00002 TABLE II Alignment of major ospC groups with ospC alleles identified by SSCP analysis Major ospC ospC allele GenBank Group (SSCP) number.sup.1 Ticks Skin.sup.2 Disseminated.sup.2 A 1 AF029860 17 23 21 B 2 AF029861 17 19 4 C 3 AF029862 11 3 0 D 4 AF029863 10 1 0 E 5, 7 AF029864 6 1 0 F 6 AF029865 9 0 0 G 8 AF029867 5 7 0 H 9 AF029868 7 6 0 I 10 AF029869 1 9 3 J 11, 18 AF029870 3 7 0 K 12, 13 AF029871 6 32 16 L -- L42899 2 0 0 M 14 U01892 1 3 0 N 15 L42899 1 3 0 O -- X84778 0 1 0 P -- U91796 1 0 0 Q -- U91790 1 0 0 R -- U91791 2 0 0 S -- U91793 1 0 0 T 16 AF065143 0 1 0 U 17 AF065144 0 2 0 .sup.1A single GenBank sequence of each type is given as an example. .sup.2The number of each major ospC group observed in blood, synovial fluid or cerebrospinal fluid. This includes both SSCP data and data from the literature, including GenBank. *B. burgdorferi sensu stricto Groups P through S are only found in Europe. Groups R and S are excluded from the analysis because nearly identical ospC alleles are found in B. afzelii and B. garinii, showing these groups were recently created by cross-species transfer.

Multiple Infections

Of the one hundred and thirty-two primary isolates from patients with Lyme disease in this study, most contained only a single strain. Seven skin isolates and one CSF isolate contained two different strains as determined by SSCP analysis, thus giving a total of one hundred and forty different strains. The ospC allele pairs found in multiply infected erythema migrans biopsy specimens were (OC1, OC12), (OC1, OC14), 2.times.(OC2, OC3), 2.times.(OC2, OC12), and (OC8, OC18). CSF isolate NY940657 contained ospC alleles OC1 and OC12. For CSF isolate 297, which was isolated in Connecticut, there were two ospC sequences published in GenBank: L42893 (SEQ ID NO:85), which is analogous to OC10 and U08284 (SEQ ID NO:86), which is analogous to OC12. The pair-wise difference of ospC sequences of both strains is 16.4%, suggesting CNS infection with two different strains in this isolate. Overall, 5.5% of all isolates described herein contained two strains. Because as many as 50% of ticks isolated in the wild are infected with multiple strains, exposure to multiple strains in a single tick bite is common, raising the possibility that different strains are differentially pathogenic.

To these one hundred forty strains for which the ospC allele was determined herein, twenty-two strains of known ospC sequence from GenBank were added to give a total of one hundred sixty-two. Fifty-one of these strains were obtained either from eastern Long Island; seventy-seven were obtained from Westchester County, N.Y., and the remainder from other endemic areas in the United States (twenty-two strains) and Europe (twelve strains). The isolates were divided into those from the site of the primary infection, the erythema migrans skin lesion (one hundred eighteen isolates), and those from secondary sites, where the infection had disseminated (forty-four isolates). This later group included, for example, twenty from cerebro-spinal fluid (CSF), twenty-three from blood, and one from synovial fluid.

Major ospC Groups in Human B. burgdorferi Isolates

Surprisingly, as described herein, the differences between ospC sequences among and between the families of B. burgdorferi sensu stricto fell into two groups. Pairs of ospC genes within the same family differed in nucleic acid sequence by less than two percent while pairs of ospC genes from separate families in nucleic acid sequence differed by more than eight percent. Wang et al., defined nineteen major ospC groups, designated A to S (Wang, I-N. et al., Genetics 151:15-30 (1999)). As described herein, two additional ospC groups are provided, designated T and U. OC16 represents major group T and OC17 represents major group U (Table I). The lowest pair-wise differences of group T and U to any other major ospC group are 16.1% and 20.5% respectively.

B. burgdorferi Clones are Differentially Pathogenic

As described herein, clones representing different ospC groups of Borrelia burgdorferi are differentially pathogenic. This is demonstrated by the differing frequencies of the various major ospC groups in ticks, in the initial infection in the skin, and in disseminated infections.

The strains in GenBank and the literature for which the ospC sequences have been determined were widely sampled from the entire geographic range of the species and were chosen irrespective of whether they were from ticks or humans. These strains gave a small but random sample of the frequencies of the major ospC groups in ticks and humans. As demonstrated herein, the frequency of the major ospC groups from human isolates was found to be significantly different from the frequency found in ticks on Long Island. Table III shows that the frequency distribution of strains from skin from eastern Long Island differ significantly from tick strains collected in the same area

TABLE-US-00003 TABLE III Major ospC groups Isolates From A B C D F G H I K Comb..sup.a Erythema migrans 13 6 2 0 0 1 0 4 16 4 lesions (N = 46) Ixodes scapularis 12 12 11 9 6 5 7 1 5 6 ticks (N = 74) .chi..sup.2 = 36.3 with 9 degrees of freedom p < 0.001 .sup.aCombined major groups are defined by individual frequencies of 0.025 or less and include groups E, J, N, O.

The analysis provided herein of all ospC groups presented in this study showed that most groups are found in both ticks and in humans (Table II). However, major groups A, B, I and K predominated in humans with A and K groups found most frequently. (FIG. 1).

The pattern of pathogenicity of the various clones as demonstrated by frequency in the primary site of infection, the skin, compared to the frequency in secondary sites revealed that only four major groups (A, B, I and K) were found in both the skin and secondary sites (compare Tables III an IV). All other major groups were found only in the skin. When all groups with three or fewer isolates are combined to give the combined group of Table IV, a 2 by 8 contingency test comparing the frequency distribution of skin versus secondary sites gives a significance of p<0.005. When no groups are combined, a 2 by 15 contingency test is still significant (.chi..sup.2=24.07 with 14 degrees of freedom, p<0.05). The distribution of strains from primary and secondary sites indicated that only a certain of the major groups, A, B, I, and K cause disseminated disease. As described herein, these are referred to as invasive clones whereas other clones are referred to as non-invasive clones.

TABLE-US-00004 TABLE IV Major ospC groups Isolates From A B G H I J K Comb..sup.a Erythema migrans 23 19 7 6 9 7 32 16 lesions (N = 118) Disseminated Infections 21 4 0 0 3 0 16 0 (N = 44) .chi..sup.2 = 23.6 with 7 degrees of freedom p < 0.005 .sup.aCombined major groups are defined by individual frequencies of 0.025 or less and include groups C, D, E, M, N, O, T and U.

As described herein, the different clones of B. burgdorferi sensu stricto, as defined by ospC groups, are differentially pathogenic. Some groups very rarely, if ever, cause human disease, e.g. ospC groups D, E, F, and L. Some groups cause a local infection at the tick bite site, but not systemic disease, e.g. ospC groups G, H, J, and T. Finally, there are some groups which are responsible for systemic disease; these are ospC groups A, B, I, and K. Our findings indicate that all systemic B. burgdorferi sensu stricto infections in humans are caused by strains in these four ospC groups.

FIG. 1 shows the frequency distribution of major ospC groups among B. burgdorferi isolates from Eastern Long Island Ixodes scapularis ticks, n=72, (A); erythema migrans lesions, n=118, (B); and secondary sites of infection, n=44, (C). The percentage of group A plus K increased from 23% in the tick isolates, to 47% in the skin isolates, and to 84% in the secondary sites. The length of the bars in FIG. 1 reflect this increase, by holding the length of the combined A and K groups constant. In the skin, groups C, D, E, M, N, O, T and U have been combined since their individual frequencies are 0.025 or less. This combination of groups when combined make up 12.7% of the total number of strains.

A similar analysis was conducted for Borrelia afzelii. The analysis included OspC alleles from 21 strains from GenBank and 12 strains sequenced for this study. These sequences fell into 20 major groups where the definition of a group is less that 1% sequence diversity within a group and at least 7.7% sequence difference between groups. There were two exceptions to this rule which were caused by a deletion in one ospC gene and a cross-species transfer of a small section of DNA in another ospC gene. When these anomalous sections were removed, all ospC alleles fell into 20 groups. Only two groups contained strains from chronic infections--groups A and B. By analogy and the B. burgdorferi study, it appears that only two groups are pathogenic in B. afzelii.

Example 2

Protein Expression and Immunoblot

Protein Expression

The Escherichia coli (strain BL21 (pLysS) or strain B834 (DE3)) were transformed with the plasmid encoding the recombinant chimeric Borrelia proteins (RCBPs), and grown in 10 ml LB media (5 g/l NaCl, 10 g/l tryptone, 5 g/l yeast extract, 25 mg/l chloramphenicol and 50 mg/l ampicillin) at 37.degree. C., with shaking. When the optical density at 600 .lamda. reached 0.3-0.4 units, recombinant protein expression was induced by adding IPTG (isopropyl B-D-thiogalactopyranoside) to a final concentration of 0.5 mM and the cells were grown for an additional three hours. The cultures were harvested by centrifugation at 3800.times.g for five minutes. The cells were resuspended in 20 mM NaPO.sub.4, pH 7.7 and stored at -20.degree. C. overnight. Once thawed, the crude extracts were incubated with DNase (2 .mu.g/ml) in the presence of 2.5 mM of MgCl.sub.2 at room temperature for thirty minutes, spun at 14000 rpm (Eppendorf 5417C) for five minutes and 5 .mu.l of the protein sample was run on a SDS-PAGE which was either stained in Commassie Blue or used for Immunoblot. Protein samples were solubilized, usually with a sodium dodecyl sulphate (SDS) containing buffer and in selected cases with reducing agents such as dithiothreitol (DTT) or 2-mercaptoethanol (2-ME). Following solubilization, the material was separated by SDS-PAGE. The proteins were then eletrophoretically transferred to a polyvinylidene difluoride membrane (PVDF, Immobilon-P.RTM., Millipore). The transfer of proteins was monitored by a reversible staining procedure, Ponceau S. The stained membrane was made and the membrane destained by soaking in water for 10 minutes. All non-specific binding sites in the proteins and on the membrane were blocked by immersing the membrane in a solution containing a protein or detergent blocking agent (5% milk in tris-buffered saline (TBS) Tween-20.RTM. 0.1%). The membranes were then incubated with primary antibody (either a monoclonal antibody or Erythema Migrans Lyme disease human serum). The membrane was washed and the antibody-antigen complexes were identified using alkaline phosphatase (AP) enzymes coupled to secondary antibody, either anti-immunoglobulin G (anti-mouse IgG) to detect the monoclonal antibody or anti-human IgA+IgG+IgM to detect the serum antibodies. A chromogenic substrate for alkaline phosphatase was then used to visualize the activity.

Example 3

Serologic Characterization--ELISA (Enzyme-Linked Immunosorbent Assay)

Immobilization of RCBPs onto ELISA Plates, Determining Optimal RCBP Binding:

A solution of purified RCBPs in sodium phosphate buffer, pH 9.0 was used to coat commercial microwell plates (MaxiSorp.RTM., Nunc). Recombinant OspC Borrelia proteins ale described in Table V. Th e coating procedure was as follows: 100 .mu.l of a solution containing the appropriate concentration of each RCBP was added to each well and the microwell plate was incubated for either one hour at room temperature or at 4.degree. C. overnight. The antigen solution was removed from the wells, the plate washed three times with phosphate buffered saline (PBS) pH 9.0, and 200 .mu.l of blocking solution added (2% BSA fraction V (Sigma) in PBS). Following a thirty minute incubation at 37.degree. C., the plates were washed three times with PBS, wrapped in plastic and stored at 4.degree. C. until used. The binding of the individual RCBPs was measured using monoclonal antibodies specific for either OspA or OspC followed (after washing) by an alkaline phosphatase-conjugated goat anti-mouse secondary antibody. The upper limit of protein binding was found to be beyond the working range of the monoclonal antibody used to measure it, and the standard blocking protocol was found to successfully saturate this high protein binding capacity, leaving low background readings in the control wells. The results of these experiments indicated that a protein concentration of 0.5 .mu.g/ml in the coating buffer was optimal for each of the RCBP tested. It was not found to be necessary that the chimeric proteins be immobilized in a specific molar ratio to one another; only that enough of each protein be bound so that epitopes in that chimeric protein do not become limiting in subsequent ELISA assays using patient serum. For practical purposes, it was found that these conditions were met when the monoclonal-capture assay reached an absorbance of about 1.5 units or greater for each mouse monoclonal antibody with a specific epitope represented in one of the chimeric proteins on the well surface. If necessary, however, the concentrations of individual proteins in the mixture can be adjusted to achieve the desired levels of immobilized protein using routine optimization. Although the amount of each RCBP bound to the surface of the well and the amount of any one epitope exposed to the solution varies somewhat from protein to protein, the amount of bound epitope was not found to be limiting within the useful range of the ELISA.

ELISA Tests:

The standard procedure for the ELISA tests was as follows: human serum samples were diluted 1:100 in specimen diluent (10% fetal bovine serum in PBS pH 9.0) and 100 .mu.l of each sample added to ELISA plate microwells that had been coated with antigen as described above. Following incubation for 1 hour at 37.degree. C., the samples were removed and the plates washed three times in TBS-Tween.TM. (0.5 M Tris pH 7.2; 1.5 M NaCl; 0.5% Tween.TM.). Coat anti-human antisera conjugated to alkaline phosphatase specific for either IgM (Fe) or IgG (Fab), (Jackson Immuno Research Laboratories) was diluted 1:1000 in PBS, pH 7.4 and 100 .mu.l of the solution added to each well. Following incubation for thirty minutes at 37.degree. C., the plates were washed three times with TBS-Tween.TM. and 100 .mu.l of substrate solution (5 mg of p-nitrophenylphosphate tablets dissolved in 1.times. diethanolamine substrate buffer to yield a 2 mg/ml solution--Kirkegaard Perry Laboratory) was added to each well. The plates were incubated for thirty minutes at 37.degree. C. and 100 .mu.l of stop solution (5% EDTA) was added to each well. The absorbance at 410 nm was read on a microplate reader (Dynatech). A sample was considered positive if it produced an average absorbance greater than the mean of the negative controls plus three standard deviations, Cross-reactivity was measured against serum from patients with syphilis, systemic lupus erythematosus, rheumatoid arthritis as well as endemic field workers and non-endemic field worker.

Using the above-described ELISA test, serum from various patients was tested. Patients with Erythema Migrans Acute (EMA) had early, localized infections, typified by the presence of well-defined erythema migrans (EM) in patients from an endemic area.

Patients with Early Disseminated (EA), are Acute Disseminated (AcD) infections were typified by EM and one of the following: additional EM lesions, AV block, neurological abnormalities (e.g., seventh nerve pasly), or meningitis. Patients with Acute Convalescent (AcC) were obtained from the same patients as EA and AcD, 2-4 weeks later. Serum was also tested from the CDC from patients with well documented Syphilis (S), serum was also obtained from SUNY at Stony Brook, Division of Rheumatology from patients with well documented systemic Lupus Erythematosus (SLE) or patients with well documented Rheumatoid Arthritis (RA). Endemic field worker sera (End), were obtained from outdoor workers from Long Island, which is endemic for Lyme disease. Non-endemic sera (Nedn) were obtained from outdoor workers from Arizona, which is not endemic for Lyme disease. In addition, serum was tested from endemic field workers (End) and non-endemic field workers (NEnd). Polypeptides of the present invention were used to test these various sera as summarized in FIG. 8.

TABLE-US-00005 TABLE V SEQ ID NO.

SEQ ID NO: Polypeptide (DNA) (POLYPEPTIDE) C2 unlipidated 5 6 C5 unlipidated 7 8 .sup.1C1 9 10 C2 11 12 C5 13 14 C7 15 16 C10 17 18 C11 19 20 C12 21 22 C1C10.sup.2 23 24 C1C12 25 26 B31C10.sup.3 27 28 B31C12 29 30 C2C7 31 32 C2C10 33 34 C2C12 35 36 C5C7 37 38 C5C10 39 40 C5C12 41 42 .sup.1C1-C12 are OspC genes/proteins with lipidation signal. .sup.2C2C10 and other compound C names refer to chimeric OspC proteins wherein the N-terminal portion of the chimera is derived from a first ospC allele and the C-terminal portion of the chimeric molecule is derived from second ospC allele, as described herein. The polypeptides were not lipidated.

Example 4

Mice Immunization with OspC Chimeric Proteins as Immunogen

Female BALB/c mice, four-five weeks old, were immunized with 5 .mu.g of OspC chimeric proteins in 100 .mu.l of aluminum hydroxide adjuvant by SC (subcutaneous) injection. Five mice were used for each group. For the negative control, five female BALB/c mice were immunized with 100 .mu.l of aluminum hydroxide adjuvant only. Two weeks after immunization, the mice received a boost with the same antigen and two weeks after that an equal boost was administered. One week after each boost, blood was drawn from each mouse (including negative controls) and the serum was tested, using the ELISA method described above, for the presence of the respective anti-OspC chimeric protein antibodies.

Mice were immunized with chimeric proteins as follows in Table VI.

TABLE-US-00006 TABLE VI Immunogen SEQIDNO.: (polypeptide) OspC Family LipCB31.sup.1 44 (DNA 43) A LipC12.sup.2 22 (DNA 21) K UnlipC2.sup.3 8 B UnlipC2C7.sup.4 32 B/E UnlipC2C10 34 B/I UnlipC2C12 36 B/K UnlipC5C10 40 E/I UnlipC5C12 42 E/K .sup.1"Lip" means lipidated N-terminus, Lip CB31 is OspC protein from B. burgdorferi strain B31. .sup.2The number immediately after "C" refers to the particular allele of OspC as described herein. .sup.3"Unlip" means the unlipidated form of the N-terminus.

Several types of single OspCs from B. burgdorferi sensu stricto, OspCB31, OspC2, OspC5, OspC7, OspC10, OspC12 and a single OspC from B. afzelii, Ctro, were used as the antigens in an ELISA to test the serum collected from the immunized mice. As shown in FIGS. 2 and 3, unlipC2C10 and unlipC2C12 elicited an immune response in the form of antibodies, (a humoral response) against a broad range of ospC families, after the first and second bleeds, respectively. The serum from unlipC2C10, unlipC2C12, LipCB31 and LipC12 immunized mice was then used to test against single OspC polypeptides from several strains of the three major Borrelia gene species Borrelia burgdorferi, Borrelia afzelii and Borrelia garinii.

As shown in FIG. 4, 13 different strains of B. burgdorferi sensu stricto (B.b.s.s.) were tested for reactivity with the above described sera. Sera from mice immunized with both LipCB31 and LipC12, which were the gold standard of this experiment, detected 12/13 of the B.b.s.s. strains tested. Sera from mice immunized with unlipidated C2C12 detected 8/13 of the strains tested. Use of unlipidated forms of these proteins as vaccine immunogens or diagnostic antigens is desirable because the product yield by the expression vector is much greater and the proteins are much easier to purify. These two reasons alone made the production of these proteins less expensive.

As shown in FIG. 5, chimeric proteins unlipC2C10 and unlipC2C12 of the present invention elicited an immune response that detected 5/6,and 6/6 of the strains tested, as compared to the gold standard lipidated proteins LipC12 and LipCB31, which detected 5/6 and 3/6 of the strains, respectively. When compared to the parental unlipidated OspC2 (rOspC2), the chimeric proteins unlipC2C10 and unlipC2C12 elicited an immune response and detected more strains than the gold standard ((0/6) versus (5/6) and (6/6) respectively). This result was unforeseen and unexpected.

In another experiment, as shown in FIGS. 6 and 7, chimeric proteins of the present invention elicited a significant immune response across all the 18 different strains of B. afzelii (FIG. 6) and all the 21 different strains of B. garinii (FIG. 7). For example, the chimeras unlipC2C10 and unlipC2C12 detected 12 and 18 of the 18 strains of B. afzelii, respectively, as compared to 0/18 detected by the parental unlipidated C2. The same chimeras detected 14 and 20 of the 21 strains of B. garinii, respectively, as compared to 0/21 detected by the parental unlipidated C2. Furthermore, the gold standards LipCB31 and LipC12 detected 2 and 17 of the 18 strains of B. afzelii, respectively, and 2 and 15 of the 21 strains of B. garinii. These results indicate that, unlike the LipOspCB31, LipOspC12 and unlipOspC2, the unlipidated C2C10 and unlipidated C2C12 used as immunogens elicited a significant immune response across all the different strains of B. burgdorferi, B. afzelii and B. garinii tested.

Additional chimeras were constructed and are listed in Table VII.

TABLE-US-00007 TABLE VII OspC Polypeptides and Chimeric Polypeptides of the Present Invention POLYPEPTIDE SEQ ID NO.: (DNA) (POLYPEPTIDES) .sup.1unlip OspC kkp(55-621*) 45 46 unlip OspC PKO 47 48 unlip OspC TRO 49 50 .sup.2unlip OspC-55B31/ 51 52 58PKO/56TRO unlip OspC2-TRO 53 54 unlip OspCB31-TRO 55 56 unlip OspCPkoCTro 57 58 .sup.3BlipOspC1C10 59 60 Blip OspC5C7 75 76 Blip OspC2C12 65 76 Blip OspC1C12 61 62 Blip OspC2C10 63 64 Blip OspC2C7 67 69 Blip OspC5C12 73 74 Blip OspC2TRO 69 70 Blip OspC5C10 71 72 Blip OspCB31TRO 77 78 Blip OspCB31C10 79 80 Blip OspCB31C12 81 82 Blip OspCPkoTro 83 84 .sup.1Ulip means the polypeptide is unlipidated. .sup.2An OspC chimera comprised of 3 OspC polypeptides. .sup.3Blip means the polypeptide is lipidated due to the gene having the OspB lipidation signal on the 5' terminus.

While this invention has been particularly shown and described with references to preferred embodiments thereof, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.

SEQUENCE LISTINGS

1

86124DNAArtificial SequencePrimer 1aaagaataca ttaagtgcga tatt 24227DNAArtificial SequencePrimer 2caatccactt aatttttgtg ttattag 27326DNAArtificial SequencePrimer 3ttgttagcag gagcttatgc aatatc 26422DNAArtificial SequencePrimer 4gggcttgtaa gctctttaac tg 225573DNAborrelia burgdorferiCDS(1)...(573) 5atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata 192Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60aaa aac gat ggt agt tta gat aat gaa gca aat cgc aac gag tca ttg 240Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 65 70 75 80tta gca gga gct tat aca ata tca acc tta ata aca caa aaa tta agt 288Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95aaa tta aac gga tca gaa ggt tta aag gaa aag att gcc gca gct aag 336Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110aaa tgc tct gaa gag ttt agt act aaa cta aaa gat aat cat gca cag 384Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125ctt ggt ata cag ggc gtt act gat gaa aat gca aaa aaa gct att tta 432Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140aaa gca aat gca gcg ggt aaa gat aag ggc gtt gaa gaa ctt gaa aag 480Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160ttg tcc gga tca tta gaa agc tta tca aaa gca gct aaa gag atg ctt 528Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175gct aat tca gtt aaa gag ctt aca agc cct gtt gtc cat gga tcc 573Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Ser 180 185 1906191PRTborrelia burgdorferi 6Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu65 70 75 80Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Ser 180 185 1907557DNABorrelia burgdorferiCDS(3)...(557) 7atg gct tgt aat aat tca gga aaa gat ggg aat gca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa gtt gag acc 144Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45tta ctt gca tct ata gat gaa ctt gct acc aaa gct att ggt aaa aaa 192Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac aca tca ttg 240Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu 65 70 75 80tta tca gga gct tat gca ata tct gac cta ata gca gaa aaa tta aat 288Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca gct aag caa 336Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat gca gtg ctt 384Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125ggt ctg gac aat ctt act gat gat aat gca caa aga gct att tta aaa 432Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa aag tta ttt 480Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca tta aaa aat 528Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175gct gtt aaa gag ctt aca agt cct att gt 557Ala Val Lys Glu Leu Thr Ser Pro Ile 180 1858185PRTBorrelia burgdorferi 8Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu65 70 75 80Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175Ala Val Lys Glu Leu Thr Ser Pro Ile 180 1859579DNABorrelia burgdorferiCDS(1)...(579) 9atg act tta ttt tta ttt ata tct tgt aat aat tca ggg aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta ctt gct 144Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu Leu Ala 35 40 45gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att gct gct 192Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala 50 55 60aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat acc gaa 240Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp Thr Glu 65 70 75 80aat aat cac aat gga tca ttg tta gcg gga gct tat gca ata tca acc 288Asn Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr 85 90 95cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta aag gaa 336Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu 100 105 110aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat aaa tta 384Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu 115 120 125aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat gct gat 432Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Ala Asp 130 135 140gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa ggt gct 480Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala145 150 155 160gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca aaa gca 528Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser Lys Ala 165 170 175gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc cct gtt 576Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val 180 185 190gtg 579Val10193PRTBorrelia burgdorferi 10Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu Leu Ala 35 40 45Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala 50 55 60Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp Thr Glu65 70 75 80Asn Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr 85 90 95Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu 100 105 110Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu 115 120 125Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Ala Asp 130 135 140Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala145 150 155 160Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser Lys Ala 165 170 175Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val 180 185 190Val11582DNABorrelia brgdorferiCDS(1)...(582) 11atg act tta ttt tta ttt ata tct tgt aat aat tca ggg aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta ctt gct 144Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu Leu Ala 35 40 45gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gag ctt gct aaa 192Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys 50 55 60gct att ggt aaa aaa ata aaa aac gat ggt agt tta gat aat gaa gca 240Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala 65 70 75 80aat cgc aac gag tca ttg tta gca gga gct tat aca ata tca acc tta 288Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu 85 90 95ata aca caa aaa tta agt aaa tta aac gga tca gaa ggt tta aag gaa 336Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu 100 105 110aag att gcc gca gct aag aaa tgc tct gaa gag ttt agt act aaa cta 384Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu 115 120 125aaa gat aat cat gca cag ctt ggt ata cag ggc gtt act gat gaa aat 432Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp Glu Asn 130 135 140gca aaa aaa gct att tta aaa gca aat gca gcg ggt aaa gat aag ggc 480Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly145 150 155 160gtt gaa gaa ctt gaa aag ttg tcc gga tca tta gaa agc tta tca aaa 528Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys 165 170 175gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc cct 576Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 190gtt gtg 582Val Val12194PRTBorrelia brgdorferi 12Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu Leu Ala 35 40 45Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys 50 55 60Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala65 70 75 80Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu 85 90 95Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu 100 105 110Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu 115 120 125Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp Glu Asn 130 135 140Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly145 150 155 160Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys 165 170 175Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 190Val Val13576DNABorrelia burgdorferiCDS(1)...(576) 13atg act tta ttt tta ttt ata tct tgt aat aat tca gga aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat gca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gcc 144Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa ctt gct acc 192Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60aaa gct att ggt aaa aaa ata ggc aat aat ggt tta gag gcc aat cag 240Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln 65 70 75 80agt aaa aac aca tca ttg tta tca gga gct tat gca ata tct gac cta 288Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu 85 90 95ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta aag gaa aag 336Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys 100 105 110att gat aca gct aag caa tgt tct aca gaa ttt act aat aaa cta aaa 384Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys 115 120 125agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat gat aat gca 432Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala 130 135 140caa aga gct att tta aaa aaa cat gca aat aaa gat aag ggt gct gca 480Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala145 150 155 160gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca aaa gca gct 528Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala 165 170 175caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt cct att gtg 576Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro Ile Val 180 185 19014192PRTBorrelia burgdorferi 14Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser

Asn Ala Val Val Leu Ala 35 40 45Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln65 70 75 80Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu 85 90 95Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys 100 105 110Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys 115 120 125Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala 130 135 140Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala145 150 155 160Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala 165 170 175Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro Ile Val 180 185 19015576DNAborrelia burgdorferiCDS(1)...(576) 15atg act tta ttt tta ttt ata tct tgt aat aat tca aga aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Arg Lys Asp Gly 1 5 10 15aat gca tct aca aat tct gcc gat gag tct gtt aaa ggg cct aat ctt 96Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gcc 144Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa ctt gct acc 192Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60aaa gct att ggt aag aaa ata ggc aat aat ggt tta gag gcc aat cag 240Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln 65 70 75 80agt aaa aac aca tca ttg tta tca gga gct tat gca ata tct gac cta 288Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu 85 90 95ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta aag gaa aag 336Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys 100 105 110att gat aca gct aag caa tgt tct aca gaa ttt act aat aaa cta aaa 384Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys 115 120 125agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat gat aat gca 432Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala 130 135 140caa aga gct att tta aaa aaa cat gca aat aaa gat aag ggt gct gca 480Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala145 150 155 160gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca aaa gca gct 528Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala 165 170 175caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt cct att gtg 576Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro Ile Val 180 185 19016192PRTborrelia burgdorferi 16Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Arg Lys Asp Gly 1 5 10 15Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln65 70 75 80Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu 85 90 95Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys 100 105 110Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys 115 120 125Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala 130 135 140Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala145 150 155 160Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala 165 170 175Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro Ile Val 180 185 19017573DNABorrelia burgdorferiCDS(1)...(573) 17atg act tta ttt tta ttt ata tct tgt aat aat tca ggg aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctc gcc 144Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45gtg aaa gaa gtt gaa act ttg ctt aca tct ata gat gag ctt gct aaa 192Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys 50 55 60gct att ggt aaa aaa ata aaa aac gat gtt agt tta gat aat gag gca 240Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala 65 70 75 80gat cac aac gga tca tta ata tca gga gca tat tta att tca aac tta 288Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu 85 90 95ata aca aaa aaa ata agt gca ata aaa gat tca gga gaa ttg aag gca 336Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala 100 105 110gaa att gaa aag gct aag aaa tgt tct gaa gaa ttt act gct aaa tta 384Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu 115 120 125aaa ggt gaa cac aca gat ctt ggt aaa gaa ggc gtt act gat gat aat 432Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn 130 135 140gca aaa aaa gcc att tta aaa aca aat aat gat aaa act aag ggc gct 480Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala145 150 155 160gat gaa ctt gaa aag tta ttt gaa tca gta aaa aac ttg tca aaa gca 528Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala 165 170 175gct aaa gag atg ctt act aat tca gtt aaa gag ctt aca agc cct 573Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 19018191PRTBorrelia burgdorferi 18Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys 50 55 60Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala65 70 75 80Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu 85 90 95Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala 100 105 110Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu 115 120 125Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn 130 135 140Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala145 150 155 160Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala 165 170 175Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 19019553DNABorrelia burgdorferiCDS(1)...(553) 19atg act tta ttt tta ttt ata tct tgt aat aat tca gga aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gct 144Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45gtg aaa gaa att gaa act ttg ctt gca tct ata gat gaa ctt gct act 192Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60aaa gct att ggt aaa aaa ata gat aac aat gct ggt ttg ggt gct gaa 240Lys Ala Ile Gly Lys Lys Ile Asp Asn Asn Ala Gly Leu Gly Ala Glu 65 70 75 80gtg ggt caa aac gga tca ttg cta gca gga gct tat gca atc tca act 288Val Gly Gln Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr 85 90 95gta ata ata gaa aaa ttg agc aca tta aaa aat gta gaa gaa tta aaa 336Val Ile Ile Glu Lys Leu Ser Thr Leu Lys Asn Val Glu Glu Leu Lys 100 105 110gaa aaa att aca aag gct aag gat tgt tct gaa aaa ttc act aaa aaa 384Glu Lys Ile Thr Lys Ala Lys Asp Cys Ser Glu Lys Phe Thr Lys Lys 115 120 125tta aaa gat agc cgc gca gag ctt ggt aaa aaa gat gcc agt gat gat 432Leu Lys Asp Ser Arg Ala Glu Leu Gly Lys Lys Asp Ala Ser Asp Asp 130 135 140gat gca aaa aaa gct att tta aaa aca aat caa gct aac gat aag ggt 480Asp Ala Lys Lys Ala Ile Leu Lys Thr Asn Gln Ala Asn Asp Lys Gly145 150 155 160gct aaa gaa ctt aaa gag tta ttt gaa gca gta gaa agc ttg tca aaa 528Ala Lys Glu Leu Lys Glu Leu Phe Glu Ala Val Glu Ser Leu Ser Lys 165 170 175gcg gct aaa gag atg cta aac aag t 553Ala Ala Lys Glu Met Leu Asn Lys 18020184PRTBorrelia burgdorferi 20Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60Lys Ala Ile Gly Lys Lys Ile Asp Asn Asn Ala Gly Leu Gly Ala Glu65 70 75 80Val Gly Gln Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr 85 90 95Val Ile Ile Glu Lys Leu Ser Thr Leu Lys Asn Val Glu Glu Leu Lys 100 105 110Glu Lys Ile Thr Lys Ala Lys Asp Cys Ser Glu Lys Phe Thr Lys Lys 115 120 125Leu Lys Asp Ser Arg Ala Glu Leu Gly Lys Lys Asp Ala Ser Asp Asp 130 135 140Asp Ala Lys Lys Ala Ile Leu Lys Thr Asn Gln Ala Asn Asp Lys Gly145 150 155 160Ala Lys Glu Leu Lys Glu Leu Phe Glu Ala Val Glu Ser Leu Ser Lys 165 170 175Ala Ala Lys Glu Met Leu Asn Lys 18021582DNABorrelia burgdorferiCDS(1)...(582) 21atg act tta ttt tta ttt ata tct tgt aat aat tca gga aaa gat ggg 48Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt 96Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gct 144Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45gtg aaa gaa att gaa act ttg ctt gca tct ata gat gaa ctt gct act 192Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60aaa gct att ggt aaa aaa ata caa caa aat ggt ggt tta gct gtc gaa 240Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu 65 70 75 80gcg ggg cat aat gga aca ttg tta gca ggt gct tat aca ata tca aaa 288Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys 85 90 95cta ata aca caa aaa tta gat gga ttg aaa aat tca gaa aaa tta aag 336Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys 100 105 110gaa aaa att gaa aat gct aag aaa tgt tct gaa gat ttt act aaa aaa 384Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys 115 120 125cta gaa gga gaa cat gcg caa ctt gga att gaa aat gtt act gat gag 432Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu 130 135 140aat gca aaa aaa gct att tta ata aca gat gca gct aaa gat aag ggc 480Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly145 150 155 160gct gca gag ctt gaa aag cta ttt aaa gca gta gaa aac ttg gca aaa 528Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys 165 170 175gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agt cct 576Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 190att gtg 582Ile Val22194PRTBorrelia burgdorferi 22Met Thr Leu Phe Leu Phe Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly 1 5 10 15Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu 20 25 30Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala 35 40 45Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr 50 55 60Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu65 70 75 80Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys 85 90 95Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys 100 105 110Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys 115 120 125Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu 130 135 140Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly145 150 155 160Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys 165 170 175Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser Pro 180 185 190Ile Val231128DNAArtificial SequenceOspC Chimera 23atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa tat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa aca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala

Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca gcc 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190atg gta aat aat tca ggg aaa gat ggg aat aca tct gca aat tct gct 624Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala 195 200 205gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa att 672Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile 210 215 220aca gaa tct aac gca gtt gtt ctc gcc gtg aaa gaa gtt gaa act ttg 720Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu225 230 235 240ctt aca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata aaa 768Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys 245 250 255aac gat gtt agt tta gat aat gag gca gat cac aac gga tca tta ata 816Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile 260 265 270tca gga gca tat tta att tca aac tta ata aca aaa aaa ata agt gca 864Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala 275 280 285ata aaa gat tca gga gaa ttg aag gca gaa att gaa aag gct aag aaa 912Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys 290 295 300tgt tct gaa gaa ttt act gct aaa tta aaa ggt gaa cac aca gat ctt 960Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu305 310 315 320ggt aaa gaa ggc gtt act gat gat aat gca aaa aaa gcc att tta aaa 1008Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys 325 330 335aca aat aat gat aaa act aag ggc gct gat gaa ctt gaa aag tta ttt 1056Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe 340 345 350gaa tca gta aaa aac ttg tca aaa gca gct aaa gag atg ctt act aat 1104Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn 355 360 365tca gtt aaa gag ctt aca agc taa 1128Ser Val Lys Glu Leu Thr Ser * 370 37524375PRTArtificial SequenceOspC Chimera 24Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala 195 200 205Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile 210 215 220Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu225 230 235 240Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys 245 250 255Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile 260 265 270Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala 275 280 285Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys 290 295 300Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu305 310 315 320Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys 325 330 335Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe 340 345 350Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn 355 360 365Ser Val Lys Glu Leu Thr Ser 370 375251124DNAArtificial SequenceOspC Chimera 25atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa tat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa aca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca gcc 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190atg gta aat aat tca gga aaa gat ggg aat aca tct gca aat tct gct 624Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala 195 200 205gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa att 672Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile 210 215 220aca gaa tct aac gca gtt gtt ctg gct gtg aaa gaa att gaa act ttg 720Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu225 230 235 240ctt gca tct ata gat gaa ctt gct act aaa gct att ggt aaa aaa ata 768Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile 245 250 255caa caa aat ggt ggt tta gct gtc gaa gcg ggg cat aat gga aca ttg 816Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu 260 265 270tta gca ggt gct tat aca ata tca aaa cta ata aca caa aaa tta gat 864Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp 275 280 285gga ttg aaa aat tca gaa aaa tta aag gaa aaa att gaa aat gct aag 912Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys 290 295 300aaa tgt tct gaa gat ttt act aaa aaa cta gaa gga gaa cat gcg caa 960Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln305 310 315 320ctt gga att gaa aat gtt act gat gag aat gca aaa aaa gct att tta 1008Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 325 330 335ata aca gat gca gct aaa gat aag ggc gct gca gag ctt gaa aag cta 1056Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu 340 345 350ttt aaa gca gta gaa aac ttg gca aaa gca gct aaa gag atg ctt gct 1104Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala 355 360 365aat tca gtt aaa gag ctt ac 1124Asn Ser Val Lys Glu Leu 37026374PRTArtificial SequenceOspC Chimera 26Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala 195 200 205Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile 210 215 220Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu225 230 235 240Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile 245 250 255Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu 260 265 270Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp 275 280 285Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys 290 295 300Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln305 310 315 320Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 325 330 335Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu 340 345 350Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala 355 360 365Asn Ser Val Lys Glu Leu 370271137DNAArtificial SequenceOspC Chimera 27atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata aat aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa aat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa gca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca aaa 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190aaa cct tcc atg gta aat aat tca ggg aaa gat ggg aat aca tct gca 624Lys Pro Ser Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala 195 200 205aat tct gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt 672Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser 210 215 220aaa aaa att aca gaa tct aac gca gtt gtt ctc gcc gtg aaa gaa gtt 720Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val225 230 235 240gaa act ttg ctt aca tct ata gat gag ctt gct aaa gct att ggt aaa 768Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys 245 250 255aaa ata aaa aac gat gtt agt tta gat aat gag gca gat cac aac gga 816Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly 260 265 270tca tta ata tca gga gca tat tta att tca aac tta ata aca aaa aaa 864Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys 275 280 285ata agt gca ata aaa gat tca gga gaa ttg aag gca gaa att gaa aag 912Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys 290 295 300gct aag aaa tgt tct gaa gaa ttt act gct aaa tta aaa ggt gaa cac 960Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His305 310 315 320aca gat ctt ggt aaa gaa ggc gtt act gat gat aat gca aaa aaa gcc 1008Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala 325 330 335att tta aaa aca aat aat gat aaa act aag ggc gct gat gaa ctt gaa 1056Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu 340 345 350aag tta ttt gaa tca gta aaa aac ttg tca aaa gca gct aaa gag atg 1104Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met 355 360 365ctt act aat tca gtt aaa gag ctt aca agc taa 1137Leu Thr Asn Ser Val Lys Glu Leu Thr Ser * 370 37528378PRTArtificial SequenceOspC Chimera 28Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Ala Asn Gly Thr Lys Thr Lys

Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190Lys Pro Ser Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala 195 200 205Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser 210 215 220Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val225 230 235 240Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys 245 250 255Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly 260 265 270Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys 275 280 285Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys 290 295 300Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His305 310 315 320Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala 325 330 335Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu 340 345 350Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met 355 360 365Leu Thr Asn Ser Val Lys Glu Leu Thr Ser 370 375291133DNAArtificial SequenceOspC Chimera 29atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata aat aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa aat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa gca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca aaa 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190aaa cct tcc atg gta aat aat tca gga aaa gat ggg aat aca tct gca 624Lys Pro Ser Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala 195 200 205aat tct gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt 672Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser 210 215 220aaa aaa att aca gaa tct aac gca gtt gtt ctg gct gtg aaa gaa att 720Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile225 230 235 240gaa act ttg ctt gca tct ata gat gaa ctt gct act aaa gct att ggt 768Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly 245 250 255aaa aaa ata caa caa aat ggt ggt tta gct gtc gaa gcg ggg cat aat 816Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn 260 265 270gga aca ttg tta gca ggt gct tat aca ata tca aaa cta ata aca caa 864Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln 275 280 285aaa tta gat gga ttg aaa aat tca gaa aaa tta aag gaa aaa att gaa 912Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu 290 295 300aat gct aag aaa tgt tct gaa gat ttt act aaa aaa cta gaa gga gaa 960Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu305 310 315 320cat gcg caa ctt gga att gaa aat gtt act gat gag aat gca aaa aaa 1008His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys 325 330 335gct att tta ata aca gat gca gct aaa gat aag ggc gct gca gag ctt 1056Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu 340 345 350gaa aag cta ttt aaa gca gta gaa aac ttg gca aaa gca gct aaa gag 1104Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu 355 360 365atg ctt gct aat tca gtt aaa gag ctt ac 1133Met Leu Ala Asn Ser Val Lys Glu Leu 370 37530377PRTArtificial SequenceOspC Chimera 30Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190Lys Pro Ser Met Val Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala 195 200 205Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser 210 215 220Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile225 230 235 240Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly 245 250 255Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn 260 265 270Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln 275 280 285Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu 290 295 300Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu305 310 315 320His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys 325 330 335Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu 340 345 350Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu 355 360 365Met Leu Ala Asn Ser Val Lys Glu Leu 370 375311112DNAArtificial SequenceOspC Chimera 31atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata 192Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60aaa aac gat ggt agt tta gat aat gaa gca aat cgc aac gag tca ttg 240Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 65 70 75 80tta gca gga gct tat aca ata tca acc tta ata aca caa aaa tta agt 288Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95aaa tta aac gga tca gaa ggt tta aag gaa aag att gcc gca gct aag 336Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110aaa tgc tct gaa gag ttt agt act aaa cta aaa gat aat cat gca cag 384Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125ctt ggt ata cag ggc gtt act gat gaa aat gca aaa aaa gct att tta 432Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140aaa gca aat gca gcg ggt aaa gat aag ggc gtt gaa gaa ctt gaa aag 480Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160ttg tcc gga tca tta gaa agc tta tca aaa gca gct aaa gag atg ctt 528Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175gct aat tca gtt aaa gag ctt aca agc cct gtt gtc cat ggt aat aat 576Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190tca aga aaa gat ggg aat gca tct aca aat tct gcc gat gag tct gtt 624Ser Arg Lys Asp Gly Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val 195 200 205aaa ggg cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac 672Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220gca gtt gtt ctg gcc gtg aaa gaa gtt gag acc tta ctt gca tct ata 720Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile225 230 235 240gat gaa ctt gct acc aaa gct att ggt aag aaa ata ggc aat aat ggt 768Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly 245 250 255tta gag gcc aat cag agt aaa aac aca tca ttg tta tca gga gct tat 816Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr 260 265 270gca ata tct gac cta ata gca gaa aaa tta aat gta ttg aaa aat gaa 864Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu 275 280 285gaa tta aag gaa aag att gat aca gct aag caa tgt tct aca gaa ttt 912Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe 290 295 300act aat aaa cta aaa agt gaa cat gca gtg ctt ggt ctg gac aat ctt 960Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu305 310 315 320act gat gat aat gca caa aga gct att tta aaa aaa cat gca aat aaa 1008Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys 325 330 335gat aag ggt gct gca gaa ctt gaa aag tta ttt aaa gcg gta gaa aac 1056Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn 340 345 350tta tca aaa gca gct caa gac aca tta aaa aat gct gtt aaa gag ctt 1104Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu 355 360 365aca agt cc 1112Thr Ser 37032370PRTArtificial SequenceOspC Chimera 32Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu65 70 75 80Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190Ser Arg Lys Asp Gly Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val 195 200 205Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile225 230 235 240Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly 245 250 255Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr 260 265 270Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu 275 280 285Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe 290 295 300Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu305 310 315 320Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys 325 330 335Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn 340 345 350Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu 355 360 365Thr Ser 370331113DNAArtificial SequenceOspC Chimera 33atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata 192Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60aaa aac gat ggt agt tta gat aat gaa gca aat cgc aac gag tca ttg 240Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 65 70 75 80tta gca gga gct tat aca ata tca acc tta ata aca caa aaa tta agt 288Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95aaa tta aac gga tca gaa ggt tta aag gaa aag att gcc gca gct aag 336Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110aaa tgc tct gaa gag ttt agt act aaa cta aaa gat aat cat gca cag 384Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125ctt ggt ata cag ggc gtt act gat gaa aat gca aaa aaa gct att tta 432Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140aaa gca aat gca gcg ggt aaa gat aag ggc gtt gaa gaa ctt gaa aag 480Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155

160ttg tcc gga tca tta gaa agc tta tca aaa gca gct aaa gag atg ctt 528Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175gct aat tca gtt aaa gag ctt aca agc cct gtt gtc cat ggt aat aat 576Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190tca ggg aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt 624Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val 195 200 205aaa ggg cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac 672Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220gca gtt gtt ctc gcc gtg aaa gaa gtt gaa act ttg ctt aca tct ata 720Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile225 230 235 240gat gag ctt gct aaa gct att ggt aaa aaa ata aaa aac gat gtt agt 768Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser 245 250 255tta gat aat gag gca gat cac aac gga tca tta ata tca gga gca tat 816Leu Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr 260 265 270tta att tca aac tta ata aca aaa aaa ata agt gca ata aaa gat tca 864Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser 275 280 285gga gaa ttg aag gca gaa att gaa aag gct aag aaa tgt tct gaa gaa 912Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu 290 295 300ttt act gct aaa tta aaa ggt gaa cac aca gat ctt ggt aaa gaa ggc 960Phe Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly305 310 315 320gtt act gat gat aat gca aaa aaa gcc att tta aaa aca aat aat gat 1008Val Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp 325 330 335aaa act aag ggc gct gat gaa ctt gaa aag tta ttt gaa tca gta aaa 1056Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys 340 345 350aac ttg tca aaa gca gct aaa gag atg ctt act aat tca gtt aaa gag 1104Asn Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu 355 360 365ctt aca agc 1113Leu Thr Ser 37034371PRTArtificial SequenceOspC Chimera 34Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu65 70 75 80Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val 195 200 205Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile225 230 235 240Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser 245 250 255Leu Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr 260 265 270Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser 275 280 285Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu 290 295 300Phe Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly305 310 315 320Val Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp 325 330 335Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys 340 345 350Asn Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu 355 360 365Leu Thr Ser 370351112DNAArtificial SequenceOspC Chimera 35atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata 192Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60aaa aac gat ggt agt tta gat aat gaa gca aat cgc aac gag tca ttg 240Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 65 70 75 80tta gca gga gct tat aca ata tca acc tta ata aca caa aaa tta agt 288Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95aaa tta aac gga tca gaa ggt tta aag gaa aag att gcc gca gct aag 336Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110aaa tgc tct gaa gag ttt agt act aaa cta aaa gat aat cat gca cag 384Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125ctt ggt ata cag ggc gtt act gat gaa aat gca aaa aaa gct att tta 432Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140aaa gca aat gca gcg ggt aaa gat aag ggc gtt gaa gaa ctt gaa aag 480Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160ttg tcc gga tca tta gaa agc tta tca aaa gca gct aaa gag atg ctt 528Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175gct aat tca gtt aaa gag ctt aca agc cct gtt gtc cat ggt aat aat 576Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190tca gga aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt 624Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val 195 200 205aaa ggg cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac 672Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220gca gtt gtt ctg gct gtg aaa gaa att gaa act ttg ctt gca tct ata 720Ala Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile225 230 235 240gat gaa ctt gct act aaa gct att ggt aaa aaa ata caa caa aat ggt 768Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly 245 250 255ggt tta gct gtc gaa gcg ggg cat aat gga aca ttg tta gca ggt gct 816Gly Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala 260 265 270tat aca ata tca aaa cta ata aca caa aaa tta gat gga ttg aaa aat 864Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn 275 280 285tca gaa aaa tta aag gaa aaa att gaa aat gct aag aaa tgt tct gaa 912Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu 290 295 300gat ttt act aaa aaa cta gaa gga gaa cat gcg caa ctt gga att gaa 960Asp Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu305 310 315 320aat gtt act gat gag aat gca aaa aaa gct att tta ata aca gat gca 1008Asn Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala 325 330 335gct aaa gat aag ggc gct gca gag ctt gaa aag cta ttt aaa gca gta 1056Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val 340 345 350gaa aac ttg gca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa 1104Glu Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys 355 360 365gag ctt ac 1112Glu Leu 37036370PRTArtificial SequenceOspC Chimera 36Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu65 70 75 80Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val 195 200 205Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn 210 215 220Ala Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile225 230 235 240Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly 245 250 255Gly Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala 260 265 270Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn 275 280 285Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu 290 295 300Asp Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu305 310 315 320Asn Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala 325 330 335Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val 340 345 350Glu Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys 355 360 365Glu Leu 370371106DNAArtificial SequenceOspC Chimera 37atg gct tgt aat aat tca gga aaa gat ggg aat gca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa gtt gag acc 144Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45tta ctt gca tct ata gat gaa ctt gct acc aaa gct att ggt aaa aaa 192Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac aca tca ttg 240Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu 65 70 75 80tta tca gga gct tat gca ata tct gac cta ata gca gaa aaa tta aat 288Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca gct aag caa 336Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat gca gtg ctt 384Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125ggt ctg gac aat ctt act gat gat aat gca caa aga gct att tta aaa 432Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa aag tta ttt 480Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca tta aaa aat 528Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175gct gtt aaa gag ctt aca agt cct att gtc cat ggt aat aat tca aga 576Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Arg 180 185 190aaa gat ggg aat gca tct aca aat tct gcc gat gag tct gtt aaa ggg 624Lys Asp Gly Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt 672Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220gtt ctg gcc gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa 720Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu225 230 235 240ctt gct acc aaa gct att ggt aag aaa ata ggc aat aat ggt tta gag 768Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu 245 250 255gcc aat cag agt aaa aac aca tca ttg tta tca gga gct tat gca ata 816Ala Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile 260 265 270tct gac cta ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta 864Ser Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu 275 280 285aag gaa aag att gat aca gct aag caa tgt tct aca gaa ttt act aat 912Lys Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn 290 295 300aaa cta aaa agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat 960Lys Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp305 310 315 320gat aat gca caa aga gct att tta aaa aaa cat gca aat aaa gat aag 1008Asp Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys 325 330 335ggt gct gca gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca 1056Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser 340 345 350aaa gca gct caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt 1104Lys Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser 355 360 365cc 110638368PRTArtificial SequenceOspC Chimera 38Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu65 70 75 80Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150

155 160Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Arg 180 185 190Lys Asp Gly Asn Ala Ser Thr Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu225 230 235 240Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu 245 250 255Ala Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile 260 265 270Ser Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu 275 280 285Lys Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn 290 295 300Lys Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp305 310 315 320Asp Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys 325 330 335Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser 340 345 350Lys Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser 355 360 365391107DNAArtificial SequenceOspC Chimera 39atg gct tgt aat aat tca gga aaa gat ggg aat gca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa gtt gag acc 144Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45tta ctt gca tct ata gat gaa ctt gct acc aaa gct att ggt aaa aaa 192Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac aca tca ttg 240Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu 65 70 75 80tta tca gga gct tat gca ata tct gac cta ata gca gaa aaa tta aat 288Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca gct aag caa 336Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat gca gtg ctt 384Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125ggt ctg gac aat ctt act gat gat aat gca caa aga gct att tta aaa 432Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa aag tta ttt 480Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca tta aaa aat 528Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175gct gtt aaa gag ctt aca agt cct att gtc cat ggt aat aat tca ggg 576Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Gly 180 185 190aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg 624Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt 672Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220gtt ctc gcc gtg aaa gaa gtt gaa act ttg ctt aca tct ata gat gag 720Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu225 230 235 240ctt gct aaa gct att ggt aaa aaa ata aaa aac gat gtt agt tta gat 768Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp 245 250 255aat gag gca gat cac aac gga tca tta ata tca gga gca tat tta att 816Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile 260 265 270tca aac tta ata aca aaa aaa ata agt gca ata aaa gat tca gga gaa 864Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu 275 280 285ttg aag gca gaa att gaa aag gct aag aaa tgt tct gaa gaa ttt act 912Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr 290 295 300gct aaa tta aaa ggt gaa cac aca gat ctt ggt aaa gaa ggc gtt act 960Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr305 310 315 320gat gat aat gca aaa aaa gcc att tta aaa aca aat aat gat aaa act 1008Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr 325 330 335aag ggc gct gat gaa ctt gaa aag tta ttt gaa tca gta aaa aac ttg 1056Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn Leu 340 345 350tca aaa gca gct aaa gag atg ctt act aat tca gtt aaa gag ctt aca 1104Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr 355 360 365agc 1107Ser40369PRTArtificial SequenceOspC Chimera 40Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu65 70 75 80Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Gly 180 185 190Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu225 230 235 240Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp 245 250 255Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile 260 265 270Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu 275 280 285Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr 290 295 300Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr305 310 315 320Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr 325 330 335Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn Leu 340 345 350Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr 355 360 365Ser411106DNAArtificial SequenceOspC Chimera 41atg gct tgt aat aat tca gga aaa gat ggg aat gca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa gtt gag acc 144Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45tta ctt gca tct ata gat gaa ctt gct acc aaa gct att ggt aaa aaa 192Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac aca tca ttg 240Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu 65 70 75 80tta tca gga gct tat gca ata tct gac cta ata gca gaa aaa tta aat 288Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca gct aag caa 336Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat gca gtg ctt 384Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125ggt ctg gac aat ctt act gat gat aat gca caa aga gct att tta aaa 432Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa aag tta ttt 480Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca tta aaa aat 528Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175gct gtt aaa gag ctt aca agt cct att gtc cat ggt aat aat tca gga 576Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Gly 180 185 190aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg 624Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt 672Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220gtt ctg gct gtg aaa gaa att gaa act ttg ctt gca tct ata gat gaa 720Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu225 230 235 240ctt gct act aaa gct att ggt aaa aaa ata caa caa aat ggt ggt tta 768Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu 245 250 255gct gtc gaa gcg ggg cat aat gga aca ttg tta gca ggt gct tat aca 816Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr 260 265 270ata tca aaa cta ata aca caa aaa tta gat gga ttg aaa aat tca gaa 864Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu 275 280 285aaa tta aag gaa aaa att gaa aat gct aag aaa tgt tct gaa gat ttt 912Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe 290 295 300act aaa aaa cta gaa gga gaa cat gcg caa ctt gga att gaa aat gtt 960Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val305 310 315 320act gat gag aat gca aaa aaa gct att tta ata aca gat gca gct aaa 1008Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys 325 330 335gat aag ggc gct gca gag ctt gaa aag cta ttt aaa gca gta gaa aac 1056Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn 340 345 350ttg gca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt 1104Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu 355 360 365ac 110642368PRTArtificial SequenceOspC Chimera 42Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Ala Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys 50 55 60Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser Leu65 70 75 80Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu Asn 85 90 95Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys Gln 100 105 110Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val Leu 115 120 125Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu Lys 130 135 140Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe145 150 155 160Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys Asn 165 170 175Ala Val Lys Glu Leu Thr Ser Pro Ile Val His Gly Asn Asn Ser Gly 180 185 190Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly 195 200 205Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val 210 215 220Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu225 230 235 240Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu 245 250 255Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr 260 265 270Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu 275 280 285Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe 290 295 300Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val305 310 315 320Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys 325 330 335Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn 340 345 350Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu 355 360 36543633DNABorrelia burgdorferiCDS(1)...(633) 43atg aaa aag aat aca tta agt gcg ata tta atg act tta ttt tta ttt 48Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15ata tct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 96Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 20 25 30gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata aat aaa aaa 144Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 35 40 45att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 192Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 50 55 60ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 240Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 65 70 75 80ata cac caa aat aat ggt ttg gat acc gaa aat aat cac aat gga tca 288Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser 85 90 95ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 336Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 100 105 110gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 384Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 115 120 125aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 432Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 130 135 140ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 480Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu145 150 155 160aaa gca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 528Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu 165 170 175ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct

576Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 180 185 190aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca aaa 624Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 195 200 205aaa cct taa 633Lys Pro * 21044210PRTBorrelia burgdorferi 44Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15Ile Ser Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 20 25 30Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 35 40 45Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 50 55 60Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys65 70 75 80Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser 85 90 95Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 100 105 110Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 115 120 125Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 130 135 140Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu145 150 155 160Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu 165 170 175Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 180 185 190Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 195 200 205Lys Pro 21045580DNABorrelia burgdorferiCDS(1)...(580) 45atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata aat aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa aat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa gca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca tcc 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ser 180 185 190atg g 580Met46193PRTBorrelia burgdorferi 46Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Asn Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Asn Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Ala Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ser 180 185 190Met47639DNABorrelia gariniiCDS(1)...(639) 47atg aaa aag aat aca tta agt gcg ata tta atg act tta ttt tta ttt 48Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15ata tct tgt agt aat tca ggg aaa ggt ggg gat tct gca tct act aat 96Ile Ser Cys Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn 20 25 30cct gct gac gag tct gcg aaa ggg cct aat ctt aca gaa ata agc aaa 144Pro Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys 35 40 45aaa att aca gat tct aat gca ttt gta ctt gct gtt aaa gaa gtt gag 192Lys Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu 50 55 60act ttg gtt tta tct ata gat gaa ctt gct aag aaa gct att ggt caa 240Thr Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln 65 70 75 80aaa ata gac aat aat aat ggt tta gct gct tta aat aat cag aat gga 288Lys Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly 85 90 95tcg ttg tta gca gga gcc tat gca ata tca acc cta ata aca gaa aaa 336Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys 100 105 110ttg agt aaa ttg aaa aat tta gaa gaa tta aag aca gaa att gca aag 384Leu Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys 115 120 125gct aag aaa tgt tcc gaa gaa ttt act aat aaa cta aaa agt ggt cat 432Ala Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His 130 135 140gca gat ctt ggc aaa cag gat gct acc gat gat cat gca aaa gca gct 480Ala Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala145 150 155 160att tta aaa aca cat gca act acc gat aaa ggt gct aaa gaa ttt aaa 528Ile Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys 165 170 175gat tta ttt gaa tca gta gaa ggt ttg tta aaa gca gct caa gta gca 576Asp Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala 180 185 190cta act aat tca gtt aaa gaa ctt aca agt cct gtt gta gca gaa agt 624Leu Thr Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser 195 200 205cca aaa aaa cct taa 639Pro Lys Lys Pro * 21048212PRTBorrelia garinii 48Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15Ile Ser Cys Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn 20 25 30Pro Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys 35 40 45Lys Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu 50 55 60Thr Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln65 70 75 80Lys Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly 85 90 95Ser Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys 100 105 110Leu Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys 115 120 125Ala Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His 130 135 140Ala Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala145 150 155 160Ile Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys 165 170 175Asp Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala 180 185 190Leu Thr Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser 195 200 205Pro Lys Lys Pro 21049624DNABorrelia afzeliiCDS(1)...(624) 49atg aaa aag aat aca tta agt gcg ata tta atg act tta ttt tta ttt 48Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15ata tct tgt aat aat tca ggt ggg gat tct gca tct act aat cct gat 96Ile Ser Cys Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp 20 25 30gag tct gca aaa gga cct aat ctt acc gta ata agc aaa aaa att aca 144Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr 35 40 45gat tct aat gca ttt tta ctg gct gtg aaa gaa gtt gag gct ttg ctt 192Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu 50 55 60tca tct ata gat gaa ctt tct aaa gct att ggt aaa aaa ata aaa aat 240Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn 65 70 75 80gat ggt act tta gat aac gaa gca aat cga aac gaa tca ttg ata gca 288Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala 85 90 95gga gct tat gaa ata tca aaa cta ata aca caa aaa tta agt gta ttg 336Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu 100 105 110aat tca gaa gaa tta aag aaa aaa att aaa gag gct aag gat tgt tcc 384Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser 115 120 125caa aaa ttt act act aag cta aaa gat agt cat gca gag ctt ggt ata 432Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile 130 135 140caa agc gtt cag gat gat aat gca aaa aaa gct att tta aaa aca cat 480Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His145 150 155 160gga act aaa gac aag ggt gct aaa gaa ctt gaa gag tta ttt aaa tca 528Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser 165 170 175cta gaa agc ttg tca aaa gca gcg caa gca gca tta act aat tca gtt 576Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val 180 185 190aaa gag ctt aca aat cct gtt gtg gca gaa agt cca aaa aaa cct taa 624Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys Lys Pro * 195 200 20550207PRTBorrelia afzelii 50Met Lys Lys Asn Thr Leu Ser Ala Ile Leu Met Thr Leu Phe Leu Phe 1 5 10 15Ile Ser Cys Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp 20 25 30Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr 35 40 45Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu 50 55 60Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn65 70 75 80Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala 85 90 95Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu 100 105 110Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser 115 120 125Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile 130 135 140Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His145 150 155 160Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser 165 170 175Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val 180 185 190Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys Lys Pro 195 200 205511680DNAospC ChimeraCDS(1)...(1680) 51atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa tat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa aca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca gcc 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190atg ggt agt aat tca ggg aaa ggt ggg gat tct gca tct act aat cct 624Met Gly Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn Pro 195 200 205gct gac gag tct gcg aaa ggg cct aat ctt aca gaa ata agc aaa aaa 672Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 210 215 220att aca gat tct aat gca ttt gta ctt gct gtt aaa gaa gtt gag act 720Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu Thr225 230 235 240ttg gtt tta tct ata gat gaa ctt gct aag aaa gct att ggt caa aaa 768Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln Lys 245 250 255ata gac aat aat aat ggt tta gct gct tta aat aat cag aat gga tcg 816Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly Ser 260 265 270ttg tta gca gga gcc tat gca ata tca acc cta ata aca gaa aaa ttg 864Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys Leu 275 280 285agt aaa ttg aaa aat tta gaa gaa tta aag aca gaa att gca aag gct 912Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys Ala 290 295 300aag aaa tgt tcc gaa gaa ttt act aat aaa cta aaa agt ggt cat gca 960Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His Ala305 310 315 320gat ctt ggc aaa cag gat gct acc gat gat cat gca aaa gca gct att 1008Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala Ile 325 330 335tta aaa aca cat gca act acc gat aaa ggt gct aaa gaa ttt aaa gat 1056Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys Asp 340

345 350tta ttt gaa tca gta gaa ggt ttg tta aaa gca gct caa gta gca cta 1104Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala Leu 355 360 365act aat tca gtt aaa gaa ctt ggt cac cgt aat aat tca ggt ggg gat 1152Thr Asn Ser Val Lys Glu Leu Gly His Arg Asn Asn Ser Gly Gly Asp 370 375 380tct gca tct act aat cct gat gag tct gca aaa gga cct aat ctt acc 1200Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr385 390 395 400gta ata agc aaa aaa att aca gat tct aat gca ttt tta ctg gct gtg 1248Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val 405 410 415aaa gaa gtt gag gct ttg ctt tca tct ata gat gaa ctt tct aaa gct 1296Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala 420 425 430att ggt aaa aaa ata aaa aat gat ggt act tta gat aac gaa gca aat 1344Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn 435 440 445cga aac gaa tca ttg ata gca gga gct tat gaa ata tca aaa cta ata 1392Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile 450 455 460aca caa aaa tta agt gta ttg aat tca gaa gaa tta aag aaa aaa att 1440Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile465 470 475 480aaa gag gct aag gat tgt tcc caa aaa ttt act act aag cta aaa gat 1488Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp 485 490 495agt cat gca gag ctt ggt ata caa agc gtt cag gat gat aat gca aaa 1536Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys 500 505 510aaa gct att tta aaa aca cat gga act aaa gac aag ggt gct aaa gaa 1584Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu 515 520 525ctt gaa gag tta ttt aaa tca cta gaa agc ttg tca aaa gca gcg caa 1632Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln 530 535 540gca gca tta act aat tca gtt aaa gag ctt aca aat cct gtt gtg gca 1680Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala545 550 555 56052560PRTospC Chimera 52Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Ala 180 185 190Met Gly Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn Pro 195 200 205Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 210 215 220Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu Thr225 230 235 240Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln Lys 245 250 255Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly Ser 260 265 270Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys Leu 275 280 285Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys Ala 290 295 300Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His Ala305 310 315 320Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala Ile 325 330 335Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys Asp 340 345 350Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala Leu 355 360 365Thr Asn Ser Val Lys Glu Leu Gly His Arg Asn Asn Ser Gly Gly Asp 370 375 380Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr385 390 395 400Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val 405 410 415Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala 420 425 430Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn 435 440 445Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile 450 455 460Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile465 470 475 480Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp 485 490 495Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys 500 505 510Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu 515 520 525Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln 530 535 540Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala545 550 555 560531137DNAospC ChimeraCDS(1)...(1137) 53atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gag ctt gct aaa gct att ggt aaa aaa ata 192Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60aaa aac gat ggt agt tta gat aat gaa gca aat cgc aac gag tca ttg 240Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 65 70 75 80tta gca gga gct tat aca ata tca acc tta ata aca caa aaa tta agt 288Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95aaa tta aac gga tca gaa ggt tta aag gaa aag att gcc gca gct aag 336Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110aaa tgc tct gaa gag ttt agt act aaa cta aaa gat aat cat gca cag 384Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125ctt ggt ata cag ggc gtt act gat gaa aat gca aaa aaa gct att tta 432Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140aaa gca aat gca gcg ggt aaa gat aag ggc gtt gaa gaa ctt gaa aag 480Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160ttg tcc gga tca tta gaa agc tta tca aaa gca gct aaa gag atg ctt 528Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175gct aat tca gtt aaa gag ctt aca agc cct gtt gtc cat ggt aat aat 576Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190tca ggt ggg gat tct gca tct act aat cct gat gag tct gca aaa gga 624Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly 195 200 205cct aat ctt acc gta ata agc aaa aaa att aca gat tct aat gca ttt 672Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe 210 215 220tta ctg gct gtg aaa gaa gtt gag gct ttg ctt tca tct ata gat gaa 720Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu225 230 235 240ctt tct aaa gct att ggt aaa aaa ata aaa aat gat ggt act tta gat 768Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp 245 250 255aac gaa gca aat cga aac gaa tca ttg ata gca gga gct tat gaa ata 816Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile 260 265 270tca aaa cta ata aca caa aaa tta agt gta ttg aat tca gaa gaa tta 864Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu 275 280 285aag aaa aaa att aaa gag gct aag gat tgt tcc caa aaa ttt act act 912Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr 290 295 300aag cta aaa gat agt cat gca gag ctt ggt ata caa agc gtt cag gat 960Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp305 310 315 320gat aat gca aaa aaa gct att tta aaa aca cat gga act aaa gac aag 1008Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys 325 330 335ggt gct aaa gaa ctt gaa gag tta ttt aaa tca cta gaa agc ttg tca 1056Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser 340 345 350aaa gca gcg caa gca gca tta act aat tca gtt aaa gag ctt aca aat 1104Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn 355 360 365cct gtt gtg gca gaa agt cca aaa aaa cct taa 1137Pro Val Val Ala Glu Ser Pro Lys Lys Pro * 370 37554378PRTospC Chimera 54Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile 50 55 60Lys Asn Asp Gly Ser Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu65 70 75 80Leu Ala Gly Ala Tyr Thr Ile Ser Thr Leu Ile Thr Gln Lys Leu Ser 85 90 95Lys Leu Asn Gly Ser Glu Gly Leu Lys Glu Lys Ile Ala Ala Ala Lys 100 105 110Lys Cys Ser Glu Glu Phe Ser Thr Lys Leu Lys Asp Asn His Ala Gln 115 120 125Leu Gly Ile Gln Gly Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu 130 135 140Lys Ala Asn Ala Ala Gly Lys Asp Lys Gly Val Glu Glu Leu Glu Lys145 150 155 160Leu Ser Gly Ser Leu Glu Ser Leu Ser Lys Ala Ala Lys Glu Met Leu 165 170 175Ala Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val His Gly Asn Asn 180 185 190Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly 195 200 205Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe 210 215 220Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu225 230 235 240Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp 245 250 255Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile 260 265 270Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu 275 280 285Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr 290 295 300Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp305 310 315 320Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys 325 330 335Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser 340 345 350Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn 355 360 365Pro Val Val Ala Glu Ser Pro Lys Lys Pro 370 375551158DNAospC ChimeraCDS(1)...(1158) 55atg gct tgt aat aat tca ggg aaa gat ggg aat aca tct gca aat tct 48Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa aaa 96Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att acg gat tct aat gcg gtt tta ctt gct gtg aaa gag gtt gaa gcg 144Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45ttg ctg tca tct ata gat gaa att gct gct aaa gct att ggt aaa aaa 192Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60ata cac caa aat aat ggt ttg gat acc gaa tat aat cac aat gga tca 240Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser 65 70 75 80ttg tta gcg gga gct tat gca ata tca acc cta ata aaa caa aaa tta 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95gat gga ttg aaa aat gaa gga tta aag gaa aaa att gat gcg gct aag 336Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110aaa tgt tct gaa aca ttt act aat aaa tta aaa gaa aaa cac aca gat 384Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125ctt ggt aaa gaa ggt gtt act gat gct gat gca aaa gaa gcc att tta 432Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140aaa aca aat ggt act aaa act aaa ggt gct gaa gaa ctt gga aaa tta 480Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160ttt gaa tca gta gag gtc ttg tca aaa gca gct aaa gag atg ctt gct 528Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175aat tca gtt aaa gag ctt aca agc cct gtt gtg gca gaa agt cca aaa 576Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190aaa cct ttc cat ggt aat aat tca ggt ggg gat tct gca tct act aat 624Lys Pro Phe His Gly Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn 195 200 205cct gat gag tct gca aaa gga cct aat ctt acc gta ata agc aaa aaa 672Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys Lys 210 215 220att aca gat tct aat gca ttt tta ctg gct gtg aaa gaa gtt gag gct 720Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu Ala225 230 235 240ttg ctt tca tct ata gat gaa ctt tct aaa gct att ggt aaa aaa ata 768Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile 245 250 255aaa aat gat ggt act tta gat aac gaa gca aat cga aac gaa tca ttg 816Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 260 265 270ata gca gga gct tat gaa ata tca aaa cta ata aca caa aaa tta agt 864Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser 275 280 285gta ttg aat tca gaa gaa tta aag aaa aaa att aaa gag gct aag gat 912Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp 290 295 300tgt tcc caa aaa ttt act act aag cta aaa gat agt cat gca gag ctt 960Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu Leu305 310 315 320ggt ata caa agc gtt cag gat gat aat gca aaa aaa gct att tta aaa 1008Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys 325 330 335aca cat gga act aaa gac aag ggt gct aaa gaa ctt gaa gag tta ttt 1056Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe 340 345 350aaa tca cta gaa agc ttg tca aaa gca gcg caa gca gca tta act aat

1104Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn 355 360 365tca gtt aaa gag ctt aca aat cct gtt gtg gca gaa agt cca aaa aaa 1152Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys Lys 370 375 380cct taa 1158Pro *38556385PRTospC Chimera 56Met Ala Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser 1 5 10 15Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Val Leu Leu Ala Val Lys Glu Val Glu Ala 35 40 45Leu Leu Ser Ser Ile Asp Glu Ile Ala Ala Lys Ala Ile Gly Lys Lys 50 55 60Ile His Gln Asn Asn Gly Leu Asp Thr Glu Tyr Asn His Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Lys Gln Lys Leu 85 90 95Asp Gly Leu Lys Asn Glu Gly Leu Lys Glu Lys Ile Asp Ala Ala Lys 100 105 110Lys Cys Ser Glu Thr Phe Thr Asn Lys Leu Lys Glu Lys His Thr Asp 115 120 125Leu Gly Lys Glu Gly Val Thr Asp Ala Asp Ala Lys Glu Ala Ile Leu 130 135 140Lys Thr Asn Gly Thr Lys Thr Lys Gly Ala Glu Glu Leu Gly Lys Leu145 150 155 160Phe Glu Ser Val Glu Val Leu Ser Lys Ala Ala Lys Glu Met Leu Ala 165 170 175Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys 180 185 190Lys Pro Phe His Gly Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn 195 200 205Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys Lys 210 215 220Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu Ala225 230 235 240Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile 245 250 255Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu 260 265 270Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser 275 280 285Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp 290 295 300Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu Leu305 310 315 320Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys 325 330 335Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe 340 345 350Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn 355 360 365Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys Lys 370 375 380Pro385571161DNAospC ChimeraCDS(1)...(1161) 57atg tgt agt aat tca ggg aaa ggt ggg gat tct gca tct act aat cct 48Met Cys Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn Pro 1 5 10 15gct gac gag tct gcg aaa ggg cct aat ctt aca gaa ata agc aaa aaa 96Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30att aca gat tct aat gca ttt gta ctt gct gtt aaa gaa gtt gag act 144Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45ttg gtt tta tct ata gat gaa ctt gct aag aaa gct att ggt caa aaa 192Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln Lys 50 55 60ata gac aat aat aat ggt tta gct gct tta aat aat cag aat gga tcg 240Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly Ser 65 70 75 80ttg tta gca gga gcc tat gca ata tca acc cta ata aca gaa aaa ttg 288Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys Leu 85 90 95agt aaa ttg aaa aat tta gaa gaa tta aag aca gaa att gca aag gct 336Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys Ala 100 105 110aag aaa tgt tcc gaa gaa ttt act aat aaa cta aaa agt ggt cat gca 384Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His Ala 115 120 125gat ctt ggc aaa cag gat gct acc gat gat cat gca aaa gca gct att 432Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala Ile 130 135 140tta aaa aca cat gca act acc gat aaa ggt gct aaa gaa ttt aaa gat 480Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys Asp145 150 155 160tta ttt gaa tca gta gaa ggt ttg tta aaa gca gct caa gta gca cta 528Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala Leu 165 170 175act aat tca gtt aaa gaa ctt aca agt cct gtt gta gca gaa agt cca 576Thr Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro 180 185 190aaa aaa cct cat atg gct aat aat tca ggt ggg gat tct gca tct act 624Lys Lys Pro His Met Ala Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr 195 200 205aat cct gat gag tct gca aaa gga cct aat ctt acc gta ata agc aaa 672Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys 210 215 220aaa att aca gat tct aat gca ttt tta ctg gct gtg aaa gaa gtt gag 720Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu225 230 235 240gct ttg ctt tca tct ata gat gaa ctt tct aaa gct att ggt aaa aaa 768Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys 245 250 255ata aaa aat gat ggt act tta gat aac gaa gca aat cga aac gaa tca 816Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser 260 265 270ttg ata gca gga gct tat gaa ata tca aaa cta ata aca caa aaa tta 864Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu 275 280 285agt gta ttg aat tca gaa gaa tta aag aaa aaa att aaa gag gct aag 912Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys 290 295 300gat tgt tcc caa aaa ttt act act aag cta aaa gat agt cat gca gag 960Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu305 310 315 320ctt ggt ata caa agc gtt cag gat gat aat gca aaa aaa gct att tta 1008Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu 325 330 335aaa aca cat gga act aaa gac aag ggt gct aaa gaa ctt gaa gag tta 1056Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu 340 345 350ttt aaa tca cta gaa agc ttg tca aaa gca gcg caa gca gca tta act 1104Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr 355 360 365aat tca gtt aaa gag ctt aca aat cct gtt gtg gca gaa agt cca aaa 1152Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys 370 375 380aaa cct taa 1161Lys Pro *38558386PRTospC Chimera 58Met Cys Ser Asn Ser Gly Lys Gly Gly Asp Ser Ala Ser Thr Asn Pro 1 5 10 15Ala Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys 20 25 30Ile Thr Asp Ser Asn Ala Phe Val Leu Ala Val Lys Glu Val Glu Thr 35 40 45Leu Val Leu Ser Ile Asp Glu Leu Ala Lys Lys Ala Ile Gly Gln Lys 50 55 60Ile Asp Asn Asn Asn Gly Leu Ala Ala Leu Asn Asn Gln Asn Gly Ser65 70 75 80Leu Leu Ala Gly Ala Tyr Ala Ile Ser Thr Leu Ile Thr Glu Lys Leu 85 90 95Ser Lys Leu Lys Asn Leu Glu Glu Leu Lys Thr Glu Ile Ala Lys Ala 100 105 110Lys Lys Cys Ser Glu Glu Phe Thr Asn Lys Leu Lys Ser Gly His Ala 115 120 125Asp Leu Gly Lys Gln Asp Ala Thr Asp Asp His Ala Lys Ala Ala Ile 130 135 140Leu Lys Thr His Ala Thr Thr Asp Lys Gly Ala Lys Glu Phe Lys Asp145 150 155 160Leu Phe Glu Ser Val Glu Gly Leu Leu Lys Ala Ala Gln Val Ala Leu 165 170 175Thr Asn Ser Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro 180 185 190Lys Lys Pro His Met Ala Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr 195 200 205Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys 210 215 220Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu225 230 235 240Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys 245 250 255Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser 260 265 270Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu 275 280 285Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys 290 295 300Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu305 310 315 320Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu 325 330 335Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu 340 345 350Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr 355 360 365Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys 370 375 380Lys Pro385591197DNAospC ChimeraCDS(1)...(1197) 59atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile 65 70 75 80gct gct aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat 288Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95acc gaa tat aat cac aat gga tca ttg tta gcg gga gct tat gca ata 336Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110tca acc cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta 384Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125aag gaa aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat 432Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140aaa tta aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat 480Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160gct gat gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa 528Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175ggt gct gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca 576Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc 624Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205cct gtt gtg gca gaa agt cca gcc atg gta aat aat tca ggg aaa gat 672Pro Val Val Ala Glu Ser Pro Ala Met Val Asn Asn Ser Gly Lys Asp 210 215 220ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat 720Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn225 230 235 240ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctc 768Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu 245 250 255gcc gtg aaa gaa gtt gaa act ttg ctt aca tct ata gat gag ctt gct 816Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala 260 265 270aaa gct att ggt aaa aaa ata aaa aac gat gtt agt tta gat aat gag 864Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu 275 280 285gca gat cac aac gga tca tta ata tca gga gca tat tta att tca aac 912Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn 290 295 300tta ata aca aaa aaa ata agt gca ata aaa gat tca gga gaa ttg aag 960Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys305 310 315 320gca gaa att gaa aag gct aag aaa tgt tct gaa gaa ttt act gct aaa 1008Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys 325 330 335tta aaa ggt gaa cac aca gat ctt ggt aaa gaa ggc gtt act gat gat 1056Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp 340 345 350aat gca aaa aaa gcc att tta aaa aca aat aat gat aaa act aag ggc 1104Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly 355 360 365gct gat gaa ctt gaa aag tta ttt gaa tca gta aaa aac ttg tca aaa 1152Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys 370 375 380gca gct aaa gag atg ctt act aat tca gtt aaa gag ctt aca agc 1197Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser385 390 39560399PRTospC Chimera 60Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile65 70 75 80Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205Pro Val Val Ala Glu Ser Pro Ala Met Val Asn Asn Ser Gly Lys Asp 210 215 220Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn225 230 235 240Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu 245 250 255Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala 260 265 270Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu 275 280 285Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn 290 295 300Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys305 310 315 320Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys 325 330 335Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp 340 345 350Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly 355 360 365Ala Asp Glu Leu

Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys 370 375 380Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser385 390 395611196DNAospC ChimeraCDS(1)...(1196) 61atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile 65 70 75 80gct gct aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat 288Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95acc gaa tat aat cac aat gga tca ttg tta gcg gga gct tat gca ata 336Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110tca acc cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta 384Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125aag gaa aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat 432Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140aaa tta aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat 480Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160gct gat gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa 528Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175ggt gct gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca 576Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc 624Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205cct gtt gtg gca gaa agt cca gcc atg gta aat aat tca gga aaa gat 672Pro Val Val Ala Glu Ser Pro Ala Met Val Asn Asn Ser Gly Lys Asp 210 215 220ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct aat 720Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn225 230 235 240ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt ctg 768Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu 245 250 255gct gtg aaa gaa att gaa act ttg ctt gca tct ata gat gaa ctt gct 816Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala 260 265 270act aaa gct att ggt aaa aaa ata caa caa aat ggt ggt tta gct gtc 864Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val 275 280 285gaa gcg ggg cat aat gga aca ttg tta gca ggt gct tat aca ata tca 912Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser 290 295 300aaa cta ata aca caa aaa tta gat gga ttg aaa aat tca gaa aaa tta 960Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu305 310 315 320aag gaa aaa att gaa aat gct aag aaa tgt tct gaa gat ttt act aaa 1008Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys 325 330 335aaa cta gaa gga gaa cat gcg caa ctt gga att gaa aat gtt act gat 1056Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp 340 345 350gag aat gca aaa aaa gct att tta ata aca gat gca gct aaa gat aag 1104Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys 355 360 365ggc gct gca gag ctt gaa aag cta ttt aaa gca gta gaa aac ttg gca 1152Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala 370 375 380aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt ac 1196Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu385 390 39562398PRTospC Chimera 62Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile65 70 75 80Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205Pro Val Val Ala Glu Ser Pro Ala Met Val Asn Asn Ser Gly Lys Asp 210 215 220Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn225 230 235 240Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu 245 250 255Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala 260 265 270Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val 275 280 285Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser 290 295 300Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu305 310 315 320Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys 325 330 335Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp 340 345 350Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys 355 360 365Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala 370 375 380Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu385 390 395631185DNAospC ChimeraCDS(1)...(1185) 63atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gag ctt 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 65 70 75 80gct aaa gct att ggt aaa aaa ata aaa aac gat ggt agt tta gat aat 288Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95gaa gca aat cgc aac gag tca ttg tta gca gga gct tat aca ata tca 336Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110acc tta ata aca caa aaa tta agt aaa tta aac gga tca gaa ggt tta 384Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125aag gaa aag att gcc gca gct aag aaa tgc tct gaa gag ttt agt act 432Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140aaa cta aaa gat aat cat gca cag ctt ggt ata cag ggc gtt act gat 480Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160gaa aat gca aaa aaa gct att tta aaa gca aat gca gcg ggt aaa gat 528Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175aag ggc gtt gaa gaa ctt gaa aag ttg tcc gga tca tta gaa agc tta 576Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190tca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca 624Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205agc cct gtt gtc cat ggt aat aat tca ggg aaa gat ggg aat aca tct 672Ser Pro Val Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser 210 215 220gca aat tct gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata 720Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240agt aaa aaa att aca gaa tct aac gca gtt gtt ctc gcc gtg aaa gaa 768Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255gtt gaa act ttg ctt aca tct ata gat gag ctt gct aaa gct att ggt 816Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly 260 265 270aaa aaa ata aaa aac gat gtt agt tta gat aat gag gca gat cac aac 864Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn 275 280 285gga tca tta ata tca gga gca tat tta att tca aac tta ata aca aaa 912Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys 290 295 300aaa ata agt gca ata aaa gat tca gga gaa ttg aag gca gaa att gaa 960Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu305 310 315 320aag gct aag aaa tgt tct gaa gaa ttt act gct aaa tta aaa ggt gaa 1008Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu 325 330 335cac aca gat ctt ggt aaa gaa ggc gtt act gat gat aat gca aaa aaa 1056His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys 340 345 350gcc att tta aaa aca aat aat gat aaa act aag ggc gct gat gaa ctt 1104Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu 355 360 365gaa aag tta ttt gaa tca gta aaa aac ttg tca aaa gca gct aaa gag 1152Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu 370 375 380atg ctt act aat tca gtt aaa gag ctt aca agc 1185Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser385 390 39564395PRTospC Chimera 64Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu65 70 75 80Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205Ser Pro Val Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser 210 215 220Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255Val Glu Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly 260 265 270Lys Lys Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn 275 280 285Gly Ser Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys 290 295 300Lys Ile Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu305 310 315 320Lys Ala Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu 325 330 335His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys 340 345 350Ala Ile Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu 355 360 365Glu Lys Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu 370 375 380Met Leu Thr Asn Ser Val Lys Glu Leu Thr Ser385 390 395651184DNAospC ChimeraCDS(1)...(1184) 65atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gag ctt 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 65 70 75 80gct aaa gct att ggt aaa aaa ata aaa aac gat ggt agt tta gat aat 288Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95gaa gca aat cgc aac gag tca ttg tta gca gga gct tat aca ata tca 336Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110acc tta ata aca caa aaa tta agt aaa tta aac gga tca gaa ggt tta 384Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125aag gaa aag att gcc gca gct aag aaa tgc tct gaa gag ttt agt act 432Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140aaa cta aaa gat aat cat gca cag ctt ggt ata cag ggc gtt act gat 480Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160gaa aat gca aaa aaa gct att tta aaa gca aat gca gcg ggt aaa gat 528Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175aag ggc gtt gaa gaa ctt gaa aag ttg tcc gga tca tta gaa agc tta 576Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190tca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca 624Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205agc cct gtt gtc cat ggt aat aat tca gga aaa gat ggg aat aca tct 672Ser Pro Val Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser 210 215 220gca aat tct gct gat

gag tct gtt aaa ggg cct aat ctt aca gaa ata 720Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gct gtg aaa gaa 768Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255att gaa act ttg ctt gca tct ata gat gaa ctt gct act aaa gct att 816Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile 260 265 270ggt aaa aaa ata caa caa aat ggt ggt tta gct gtc gaa gcg ggg cat 864Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His 275 280 285aat gga aca ttg tta gca ggt gct tat aca ata tca aaa cta ata aca 912Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr 290 295 300caa aaa tta gat gga ttg aaa aat tca gaa aaa tta aag gaa aaa att 960Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile305 310 315 320gaa aat gct aag aaa tgt tct gaa gat ttt act aaa aaa cta gaa gga 1008Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly 325 330 335gaa cat gcg caa ctt gga att gaa aat gtt act gat gag aat gca aaa 1056Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys 340 345 350aaa gct att tta ata aca gat gca gct aaa gat aag ggc gct gca gag 1104Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu 355 360 365ctt gaa aag cta ttt aaa gca gta gaa aac ttg gca aaa gca gct aaa 1152Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys 370 375 380gag atg ctt gct aat tca gtt aaa gag ctt ac 1184Glu Met Leu Ala Asn Ser Val Lys Glu Leu385 39066394PRTospC Chimera 66Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu65 70 75 80Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205Ser Pro Val Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser 210 215 220Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255Ile Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile 260 265 270Gly Lys Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His 275 280 285Asn Gly Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr 290 295 300Gln Lys Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile305 310 315 320Glu Asn Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly 325 330 335Glu His Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys 340 345 350Lys Ala Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu 355 360 365Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys 370 375 380Glu Met Leu Ala Asn Ser Val Lys Glu Leu385 390671184DNAospC ChimeraCDS(1)...(1184) 67atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gag ctt 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 65 70 75 80gct aaa gct att ggt aaa aaa ata aaa aac gat ggt agt tta gat aat 288Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95gaa gca aat cgc aac gag tca ttg tta gca gga gct tat aca ata tca 336Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110acc tta ata aca caa aaa tta agt aaa tta aac gga tca gaa ggt tta 384Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125aag gaa aag att gcc gca gct aag aaa tgc tct gaa gag ttt agt act 432Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140aaa cta aaa gat aat cat gca cag ctt ggt ata cag ggc gtt act gat 480Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160gaa aat gca aaa aaa gct att tta aaa gca aat gca gcg ggt aaa gat 528Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175aag ggc gtt gaa gaa ctt gaa aag ttg tcc gga tca tta gaa agc tta 576Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190tca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca 624Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205agc cct gtt gtc cat ggt aat aat tca aga aaa gat ggg aat gca tct 672Ser Pro Val Val His Gly Asn Asn Ser Arg Lys Asp Gly Asn Ala Ser 210 215 220aca aat tct gcc gat gag tct gtt aaa ggg cct aat ctt aca gaa ata 720Thr Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240agt aaa aaa att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa 768Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255gtt gag acc tta ctt gca tct ata gat gaa ctt gct acc aaa gct att 816Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile 260 265 270ggt aag aaa ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac 864Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn 275 280 285aca tca ttg tta tca gga gct tat gca ata tct gac cta ata gca gaa 912Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu 290 295 300aaa tta aat gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca 960Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr305 310 315 320gct aag caa tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat 1008Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His 325 330 335gca gtg ctt ggt ctg gac aat ctt act gat gat aat gca caa aga gct 1056Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala 340 345 350att tta aaa aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa 1104Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu 355 360 365aag tta ttt aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca 1152Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr 370 375 380tta aaa aat gct gtt aaa gag ctt aca agt cc 1184Leu Lys Asn Ala Val Lys Glu Leu Thr Ser385 39068394PRTospC Chimera 68Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu65 70 75 80Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205Ser Pro Val Val His Gly Asn Asn Ser Arg Lys Asp Gly Asn Ala Ser 210 215 220Thr Asn Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile225 230 235 240Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu 245 250 255Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile 260 265 270Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn 275 280 285Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu 290 295 300Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr305 310 315 320Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His 325 330 335Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala 340 345 350Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu 355 360 365Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr 370 375 380Leu Lys Asn Ala Val Lys Glu Leu Thr Ser385 390691209DNAospC ChimeraCDS(1)...(1209) 69atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gag ctt 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 65 70 75 80gct aaa gct att ggt aaa aaa ata aaa aac gat ggt agt tta gat aat 288Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95gaa gca aat cgc aac gag tca ttg tta gca gga gct tat aca ata tca 336Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110acc tta ata aca caa aaa tta agt aaa tta aac gga tca gaa ggt tta 384Thr Leu Ile Thr Gln Lys Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125aag gaa aag att gcc gca gct aag aaa tgc tct gaa gag ttt agt act 432Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140aaa cta aaa gat aat cat gca cag ctt ggt ata cag ggc gtt act gat 480Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160gaa aat gca aaa aaa gct att tta aaa gca aat gca gcg ggt aaa gat 528Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175aag ggc gtt gaa gaa ctt gaa aag ttg tcc gga tca tta gaa agc tta 576Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190tca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca 624Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205agc cct gtt gtc cat ggt aat aat tca ggt ggg gat tct gca tct act 672Ser Pro Val Val His Gly Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr 210 215 220aat cct gat gag tct gca aaa gga cct aat ctt acc gta ata agc aaa 720Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys225 230 235 240aaa att aca gat tct aat gca ttt tta ctg gct gtg aaa gaa gtt gag 768Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu 245 250 255gct ttg ctt tca tct ata gat gaa ctt tct aaa gct att ggt aaa aaa 816Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys 260 265 270ata aaa aat gat ggt act tta gat aac gaa gca aat cga aac gaa tca 864Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser 275 280 285ttg ata gca gga gct tat gaa ata tca aaa cta ata aca caa aaa tta 912Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu 290 295 300agt gta ttg aat tca gaa gaa tta aag aaa aaa att aaa gag gct aag 960Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys305 310 315 320gat tgt tcc caa aaa ttt act act aag cta aaa gat agt cat gca gag 1008Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu 325 330 335ctt ggt ata caa agc gtt cag gat gat aat gca aaa aaa gct att tta 1056Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu 340 345 350aaa aca cat gga act aaa gac aag ggt gct aaa gaa ctt gaa gag tta 1104Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu 355 360 365ttt aaa tca cta gaa agc ttg tca aaa gca gcg caa gca gca tta act 1152Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr 370 375 380aat tca gtt aaa gag ctt aca aat cct gtt gtg gca gaa agt cca aaa 1200Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys385 390 395 400aaa cct taa 1209Lys Pro *70402PRTospC Chimera 70Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu65 70 75 80Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Ser Leu Asp Asn 85 90 95Glu Ala Asn Arg Asn Glu Ser Leu Leu Ala Gly Ala Tyr Thr Ile Ser 100 105 110Thr Leu Ile Thr Gln Lys

Leu Ser Lys Leu Asn Gly Ser Glu Gly Leu 115 120 125Lys Glu Lys Ile Ala Ala Ala Lys Lys Cys Ser Glu Glu Phe Ser Thr 130 135 140Lys Leu Lys Asp Asn His Ala Gln Leu Gly Ile Gln Gly Val Thr Asp145 150 155 160Glu Asn Ala Lys Lys Ala Ile Leu Lys Ala Asn Ala Ala Gly Lys Asp 165 170 175Lys Gly Val Glu Glu Leu Glu Lys Leu Ser Gly Ser Leu Glu Ser Leu 180 185 190Ser Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr 195 200 205Ser Pro Val Val His Gly Asn Asn Ser Gly Gly Asp Ser Ala Ser Thr 210 215 220Asn Pro Asp Glu Ser Ala Lys Gly Pro Asn Leu Thr Val Ile Ser Lys225 230 235 240Lys Ile Thr Asp Ser Asn Ala Phe Leu Leu Ala Val Lys Glu Val Glu 245 250 255Ala Leu Leu Ser Ser Ile Asp Glu Leu Ser Lys Ala Ile Gly Lys Lys 260 265 270Ile Lys Asn Asp Gly Thr Leu Asp Asn Glu Ala Asn Arg Asn Glu Ser 275 280 285Leu Ile Ala Gly Ala Tyr Glu Ile Ser Lys Leu Ile Thr Gln Lys Leu 290 295 300Ser Val Leu Asn Ser Glu Glu Leu Lys Lys Lys Ile Lys Glu Ala Lys305 310 315 320Asp Cys Ser Gln Lys Phe Thr Thr Lys Leu Lys Asp Ser His Ala Glu 325 330 335Leu Gly Ile Gln Ser Val Gln Asp Asp Asn Ala Lys Lys Ala Ile Leu 340 345 350Lys Thr His Gly Thr Lys Asp Lys Gly Ala Lys Glu Leu Glu Glu Leu 355 360 365Phe Lys Ser Leu Glu Ser Leu Ser Lys Ala Ala Gln Ala Ala Leu Thr 370 375 380Asn Ser Val Lys Glu Leu Thr Asn Pro Val Val Ala Glu Ser Pro Lys385 390 395 400Lys Pro711179DNAospC ChimeraCDS(1)...(1179) 71atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca gga aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat gca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60ctg gcc gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa ctt 240Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu 65 70 75 80gct acc aaa gct att ggt aaa aaa ata ggc aat aat ggt tta gag gcc 288Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95aat cag agt aaa aac aca tca ttg tta tca gga gct tat gca ata tct 336Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110gac cta ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta aag 384Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125gaa aag att gat aca gct aag caa tgt tct aca gaa ttt act aat aaa 432Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140cta aaa agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat gat 480Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160aat gca caa aga gct att tta aaa aaa cat gca aat aaa gat aag ggt 528Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175gct gca gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca aaa 576Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190gca gct caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt cct 624Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205att gtc cat ggt aat aat tca ggg aaa gat ggg aat aca tct gca aat 672Ile Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn 210 215 220tct gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa 720Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240aaa att aca gaa tct aac gca gtt gtt ctc gcc gtg aaa gaa gtt gaa 768Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu 245 250 255act ttg ctt aca tct ata gat gag ctt gct aaa gct att ggt aaa aaa 816Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys 260 265 270ata aaa aac gat gtt agt tta gat aat gag gca gat cac aac gga tca 864Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly Ser 275 280 285tta ata tca gga gca tat tta att tca aac tta ata aca aaa aaa ata 912Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile 290 295 300agt gca ata aaa gat tca gga gaa ttg aag gca gaa att gaa aag gct 960Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala305 310 315 320aag aaa tgt tct gaa gaa ttt act gct aaa tta aaa ggt gaa cac aca 1008Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His Thr 325 330 335gat ctt ggt aaa gaa ggc gtt act gat gat aat gca aaa aaa gcc att 1056Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala Ile 340 345 350tta aaa aca aat aat gat aaa act aag ggc gct gat gaa ctt gaa aag 1104Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys 355 360 365tta ttt gaa tca gta aaa aac ttg tca aaa gca gct aaa gag atg ctt 1152Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met Leu 370 375 380act aat tca gtt aaa gag ctt aca agc 1179Thr Asn Ser Val Lys Glu Leu Thr Ser385 39072393PRTospC Chimera 72Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu65 70 75 80Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205Ile Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn 210 215 220Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu 245 250 255Thr Leu Leu Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys 260 265 270Ile Lys Asn Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly Ser 275 280 285Leu Ile Ser Gly Ala Tyr Leu Ile Ser Asn Leu Ile Thr Lys Lys Ile 290 295 300Ser Ala Ile Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala305 310 315 320Lys Lys Cys Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His Thr 325 330 335Asp Leu Gly Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala Ile 340 345 350Leu Lys Thr Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys 355 360 365Leu Phe Glu Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met Leu 370 375 380Thr Asn Ser Val Lys Glu Leu Thr Ser385 390731178DNAospC ChimeraCDS(1)...(1178) 73atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca gga aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat gca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60ctg gcc gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa ctt 240Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu 65 70 75 80gct acc aaa gct att ggt aaa aaa ata ggc aat aat ggt tta gag gcc 288Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95aat cag agt aaa aac aca tca ttg tta tca gga gct tat gca ata tct 336Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110gac cta ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta aag 384Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125gaa aag att gat aca gct aag caa tgt tct aca gaa ttt act aat aaa 432Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140cta aaa agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat gat 480Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160aat gca caa aga gct att tta aaa aaa cat gca aat aaa gat aag ggt 528Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175gct gca gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca aaa 576Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190gca gct caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt cct 624Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205att gtc cat ggt aat aat tca gga aaa gat ggg aat aca tct gca aat 672Ile Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn 210 215 220tct gct gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa 720Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240aaa att aca gaa tct aac gca gtt gtt ctg gct gtg aaa gaa att gaa 768Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile Glu 245 250 255act ttg ctt gca tct ata gat gaa ctt gct act aaa gct att ggt aaa 816Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys 260 265 270aaa ata caa caa aat ggt ggt tta gct gtc gaa gcg ggg cat aat gga 864Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn Gly 275 280 285aca ttg tta gca ggt gct tat aca ata tca aaa cta ata aca caa aaa 912Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys 290 295 300tta gat gga ttg aaa aat tca gaa aaa tta aag gaa aaa att gaa aat 960Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn305 310 315 320gct aag aaa tgt tct gaa gat ttt act aaa aaa cta gaa gga gaa cat 1008Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu His 325 330 335gcg caa ctt gga att gaa aat gtt act gat gag aat gca aaa aaa gct 1056Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys Ala 340 345 350att tta ata aca gat gca gct aaa gat aag ggc gct gca gag ctt gaa 1104Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu 355 360 365aag cta ttt aaa gca gta gaa aac ttg gca aaa gca gct aaa gag atg 1152Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu Met 370 375 380ctt gct aat tca gtt aaa gag ctt ac 1178Leu Ala Asn Ser Val Lys Glu Leu385 39074392PRTospC Chimera 74Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu65 70 75 80Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205Ile Val His Gly Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn 210 215 220Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Ile Glu 245 250 255Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys 260 265 270Lys Ile Gln Gln Asn Gly Gly Leu Ala Val Glu Ala Gly His Asn Gly 275 280 285Thr Leu Leu Ala Gly Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys 290 295 300Leu Asp Gly Leu Lys Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn305 310 315 320Ala Lys Lys Cys Ser Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu His 325 330 335Ala Gln Leu Gly Ile Glu Asn Val Thr Asp Glu Asn Ala Lys Lys Ala 340 345 350Ile Leu Ile Thr Asp Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu 355 360 365Lys Leu Phe Lys Ala Val Glu Asn Leu Ala Lys Ala Ala Lys Glu Met 370 375 380Leu Ala Asn Ser Val Lys Glu Leu385 390751178DNAospC ChimeraCDS(1)...(1178) 75atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca gga aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat gca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca gtt gtt 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60ctg gcc gtg aaa gaa gtt gag acc tta ctt gca tct ata gat gaa ctt 240Leu Ala Val Lys Glu Val

Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu 65 70 75 80gct acc aaa gct att ggt aaa aaa ata ggc aat aat ggt tta gag gcc 288Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95aat cag agt aaa aac aca tca ttg tta tca gga gct tat gca ata tct 336Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110gac cta ata gca gaa aaa tta aat gta ttg aaa aat gaa gaa tta aag 384Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125gaa aag att gat aca gct aag caa tgt tct aca gaa ttt act aat aaa 432Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140cta aaa agt gaa cat gca gtg ctt ggt ctg gac aat ctt act gat gat 480Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160aat gca caa aga gct att tta aaa aaa cat gca aat aaa gat aag ggt 528Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175gct gca gaa ctt gaa aag tta ttt aaa gcg gta gaa aac tta tca aaa 576Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190gca gct caa gac aca tta aaa aat gct gtt aaa gag ctt aca agt cct 624Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205att gtc cat ggt aat aat tca aga aaa gat ggg aat gca tct aca aat 672Ile Val His Gly Asn Asn Ser Arg Lys Asp Gly Asn Ala Ser Thr Asn 210 215 220tct gcc gat gag tct gtt aaa ggg cct aat ctt aca gaa ata agt aaa 720Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240aaa att aca gaa tct aac gca gtt gtt ctg gcc gtg aaa gaa gtt gag 768Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu 245 250 255acc tta ctt gca tct ata gat gaa ctt gct acc aaa gct att ggt aag 816Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys 260 265 270aaa ata ggc aat aat ggt tta gag gcc aat cag agt aaa aac aca tca 864Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser 275 280 285ttg tta tca gga gct tat gca ata tct gac cta ata gca gaa aaa tta 912Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu 290 295 300aat gta ttg aaa aat gaa gaa tta aag gaa aag att gat aca gct aag 960Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys305 310 315 320caa tgt tct aca gaa ttt act aat aaa cta aaa agt gaa cat gca gtg 1008Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val 325 330 335ctt ggt ctg gac aat ctt act gat gat aat gca caa aga gct att tta 1056Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu 340 345 350aaa aaa cat gca aat aaa gat aag ggt gct gca gaa ctt gaa aag tta 1104Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu 355 360 365ttt aaa gcg gta gaa aac tta tca aaa gca gct caa gac aca tta aaa 1152Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys 370 375 380aat gct gtt aaa gag ctt aca agt cc 1178Asn Ala Val Lys Glu Leu Thr Ser385 39076392PRTospC Chimera 76Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Ala Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala Val Val 50 55 60Leu Ala Val Lys Glu Val Glu Thr Leu Leu Ala Ser Ile Asp Glu Leu65 70 75 80Ala Thr Lys Ala Ile Gly Lys Lys Ile Gly Asn Asn Gly Leu Glu Ala 85 90 95Asn Gln Ser Lys Asn Thr Ser Leu Leu Ser Gly Ala Tyr Ala Ile Ser 100 105 110Asp Leu Ile Ala Glu Lys Leu Asn Val Leu Lys Asn Glu Glu Leu Lys 115 120 125Glu Lys Ile Asp Thr Ala Lys Gln Cys Ser Thr Glu Phe Thr Asn Lys 130 135 140Leu Lys Ser Glu His Ala Val Leu Gly Leu Asp Asn Leu Thr Asp Asp145 150 155 160Asn Ala Gln Arg Ala Ile Leu Lys Lys His Ala Asn Lys Asp Lys Gly 165 170 175Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu Asn Leu Ser Lys 180 185 190Ala Ala Gln Asp Thr Leu Lys Asn Ala Val Lys Glu Leu Thr Ser Pro 195 200 205Ile Val His Gly Asn Asn Ser Arg Lys Asp Gly Asn Ala Ser Thr Asn 210 215 220Ser Ala Asp Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys225 230 235 240Lys Ile Thr Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu 245 250 255Thr Leu Leu Ala Ser Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys 260 265 270Lys Ile Gly Asn Asn Gly Leu Glu Ala Asn Gln Ser Lys Asn Thr Ser 275 280 285Leu Leu Ser Gly Ala Tyr Ala Ile Ser Asp Leu Ile Ala Glu Lys Leu 290 295 300Asn Val Leu Lys Asn Glu Glu Leu Lys Glu Lys Ile Asp Thr Ala Lys305 310 315 320Gln Cys Ser Thr Glu Phe Thr Asn Lys Leu Lys Ser Glu His Ala Val 325 330 335Leu Gly Leu Asp Asn Leu Thr Asp Asp Asn Ala Gln Arg Ala Ile Leu 340 345 350Lys Lys His Ala Asn Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu 355 360 365Phe Lys Ala Val Glu Asn Leu Ser Lys Ala Ala Gln Asp Thr Leu Lys 370 375 380Asn Ala Val Lys Glu Leu Thr Ser385 390771230DNAospC ChimeraCDS(1)...(1230) 77atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile 65 70 75 80gct gct aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat 288Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95acc gaa tat aat cac aat gga tca ttg tta gcg gga gct tat gca ata 336Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110tca acc cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta 384Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125aag gaa aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat 432Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140aaa tta aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat 480Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160gct gat gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa 528Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175ggt gct gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca 576Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc 624Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205cct gtt gtg gca gaa agt cca aaa aaa cct ttc cat ggt aat aat tca 672Pro Val Val Ala Glu Ser Pro Lys Lys Pro Phe His Gly Asn Asn Ser 210 215 220ggt ggg gat tct gca tct act aat cct gat gag tct gca aaa gga cct 720Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly Pro225 230 235 240aat ctt acc gta ata agc aaa aaa att aca gat tct aat gca ttt tta 768Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe Leu 245 250 255ctg gct gtg aaa gaa gtt gag gct ttg ctt tca tct ata gat gaa ctt 816Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 260 265 270tct aaa gct att ggt aaa aaa ata aaa aat gat ggt act tta gat aac 864Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp Asn 275 280 285gaa gca aat cga aac gaa tca ttg ata gca gga gct tat gaa ata tca 912Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile Ser 290 295 300aaa cta ata aca caa aaa tta agt gta ttg aat tca gaa gaa tta aag 960Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu Lys305 310 315 320aaa aaa att aaa gag gct aag gat tgt tcc caa aaa ttt act act aag 1008Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr Lys 325 330 335cta aaa gat agt cat gca gag ctt ggt ata caa agc gtt cag gat gat 1056Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp Asp 340 345 350aat gca aaa aaa gct att tta aaa aca cat gga act aaa gac aag ggt 1104Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys Gly 355 360 365gct aaa gaa ctt gaa gag tta ttt aaa tca cta gaa agc ttg tca aaa 1152Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser Lys 370 375 380gca gcg caa gca gca tta act aat tca gtt aaa gag ctt aca aat cct 1200Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn Pro385 390 395 400gtt gtg gca gaa agt cca aaa aaa cct taa 1230Val Val Ala Glu Ser Pro Lys Lys Pro * 40578409PRTospC Chimera 78Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile65 70 75 80Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205Pro Val Val Ala Glu Ser Pro Lys Lys Pro Phe His Gly Asn Asn Ser 210 215 220Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys Gly Pro225 230 235 240Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe Leu 245 250 255Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Leu 260 265 270Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu Asp Asn 275 280 285Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu Ile Ser 290 295 300Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu Leu Lys305 310 315 320Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr Thr Lys 325 330 335Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln Asp Asp 340 345 350Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp Lys Gly 355 360 365Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu Ser Lys 370 375 380Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr Asn Pro385 390 395 400Val Val Ala Glu Ser Pro Lys Lys Pro 405791209DNAospC ChimeraCDS(1)...(1209) 79atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile 65 70 75 80gct gct aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat 288Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95acc gaa tat aat cac aat gga tca ttg tta gcg gga gct tat gca ata 336Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110tca acc cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta 384Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125aag gaa aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat 432Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140aaa tta aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat 480Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160gct gat gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa 528Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175ggt gct gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca 576Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc 624Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205cct gtt gtg gca gaa agt cca aaa aaa cct tcc atg gta aat aat tca 672Pro Val Val Ala Glu Ser Pro Lys Lys Pro Ser Met Val Asn Asn Ser 210 215 220ggg aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa 720Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys225 230 235 240ggg cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca 768Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala 245 250 255gtt gtt ctc gcc gtg aaa gaa gtt gaa act ttg ctt aca tct ata gat 816Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp 260 265 270gag ctt gct aaa gct att ggt aaa aaa ata aaa aac gat gtt agt tta 864Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu 275 280 285gat aat gag gca gat cac aac gga tca tta ata tca gga gca tat tta 912Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu 290 295

300att tca aac tta ata aca aaa aaa ata agt gca ata aaa gat tca gga 960Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly305 310 315 320gaa ttg aag gca gaa att gaa aag gct aag aaa tgt tct gaa gaa ttt 1008Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe 325 330 335act gct aaa tta aaa ggt gaa cac aca gat ctt ggt aaa gaa ggc gtt 1056Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val 340 345 350act gat gat aat gca aaa aaa gcc att tta aaa aca aat aat gat aaa 1104Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys 355 360 365act aag ggc gct gat gaa ctt gaa aag tta ttt gaa tca gta aaa aac 1152Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn 370 375 380ttg tca aaa gca gct aaa gag atg ctt act aat tca gtt aaa gag ctt 1200Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu385 390 395 400aca agc taa 1209Thr Ser *80402PRTospC Chimera 80Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile65 70 75 80Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205Pro Val Val Ala Glu Ser Pro Lys Lys Pro Ser Met Val Asn Asn Ser 210 215 220Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys225 230 235 240Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala 245 250 255Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu Thr Ser Ile Asp 260 265 270Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Val Ser Leu 275 280 285Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser Gly Ala Tyr Leu 290 295 300Ile Ser Asn Leu Ile Thr Lys Lys Ile Ser Ala Ile Lys Asp Ser Gly305 310 315 320Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys Ser Glu Glu Phe 325 330 335Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly Lys Glu Gly Val 340 345 350Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr Asn Asn Asp Lys 355 360 365Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu Ser Val Lys Asn 370 375 380Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser Val Lys Glu Leu385 390 395 400Thr Ser811205DNAospC ChimeraCDS(1)...(1205) 81atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt aat aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa ggg cct 144Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45aat ctt aca gaa ata agt aaa aaa att acg gat tct aat gcg gtt tta 192Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60ctt gct gtg aaa gag gtt gaa gcg ttg ctg tca tct ata gat gaa att 240Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile 65 70 75 80gct gct aaa gct att ggt aaa aaa ata cac caa aat aat ggt ttg gat 288Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95acc gaa tat aat cac aat gga tca ttg tta gcg gga gct tat gca ata 336Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110tca acc cta ata aaa caa aaa tta gat gga ttg aaa aat gaa gga tta 384Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125aag gaa aaa att gat gcg gct aag aaa tgt tct gaa aca ttt act aat 432Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140aaa tta aaa gaa aaa cac aca gat ctt ggt aaa gaa ggt gtt act gat 480Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160gct gat gca aaa gaa gcc att tta aaa aca aat ggt act aaa act aaa 528Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175ggt gct gaa gaa ctt gga aaa tta ttt gaa tca gta gag gtc ttg tca 576Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag ctt aca agc 624Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205cct gtt gtg gca gaa agt cca aaa aaa cct tcc atg gta aat aat tca 672Pro Val Val Ala Glu Ser Pro Lys Lys Pro Ser Met Val Asn Asn Ser 210 215 220gga aaa gat ggg aat aca tct gca aat tct gct gat gag tct gtt aaa 720Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys225 230 235 240ggg cct aat ctt aca gaa ata agt aaa aaa att aca gaa tct aac gca 768Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala 245 250 255gtt gtt ctg gct gtg aaa gaa att gaa act ttg ctt gca tct ata gat 816Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp 260 265 270gaa ctt gct act aaa gct att ggt aaa aaa ata caa caa aat ggt ggt 864Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly 275 280 285tta gct gtc gaa gcg ggg cat aat gga aca ttg tta gca ggt gct tat 912Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr 290 295 300aca ata tca aaa cta ata aca caa aaa tta gat gga ttg aaa aat tca 960Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser305 310 315 320gaa aaa tta aag gaa aaa att gaa aat gct aag aaa tgt tct gaa gat 1008Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp 325 330 335ttt act aaa aaa cta gaa gga gaa cat gcg caa ctt gga att gaa aat 1056Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn 340 345 350gtt act gat gag aat gca aaa aaa gct att tta ata aca gat gca gct 1104Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala 355 360 365aaa gat aag ggc gct gca gag ctt gaa aag cta ttt aaa gca gta gaa 1152Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu 370 375 380aac ttg gca aaa gca gct aaa gag atg ctt gct aat tca gtt aaa gag 1200Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu385 390 395 400ctt ac 1205Leu82401PRTospC Chimera 82Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Asn Asn Ser Gly Lys 20 25 30Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys Gly Pro 35 40 45Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Val Leu 50 55 60Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp Glu Ile65 70 75 80Ala Ala Lys Ala Ile Gly Lys Lys Ile His Gln Asn Asn Gly Leu Asp 85 90 95Thr Glu Tyr Asn His Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala Ile 100 105 110Ser Thr Leu Ile Lys Gln Lys Leu Asp Gly Leu Lys Asn Glu Gly Leu 115 120 125Lys Glu Lys Ile Asp Ala Ala Lys Lys Cys Ser Glu Thr Phe Thr Asn 130 135 140Lys Leu Lys Glu Lys His Thr Asp Leu Gly Lys Glu Gly Val Thr Asp145 150 155 160Ala Asp Ala Lys Glu Ala Ile Leu Lys Thr Asn Gly Thr Lys Thr Lys 165 170 175Gly Ala Glu Glu Leu Gly Lys Leu Phe Glu Ser Val Glu Val Leu Ser 180 185 190Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu Leu Thr Ser 195 200 205Pro Val Val Ala Glu Ser Pro Lys Lys Pro Ser Met Val Asn Asn Ser 210 215 220Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser Val Lys225 230 235 240Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser Asn Ala 245 250 255Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser Ile Asp 260 265 270Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn Gly Gly 275 280 285Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly Ala Tyr 290 295 300Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys Asn Ser305 310 315 320Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser Glu Asp 325 330 335Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile Glu Asn 340 345 350Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp Ala Ala 355 360 365Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala Val Glu 370 375 380Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val Lys Glu385 390 395 400Leu831236DNAospC ChimeraCDS(1)...(1236) 83atg aga tta tta ata gga ttt gct tta gcg tta gct tta ata gga tgt 48Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15gca caa aaa ggt gct gag tca att gga tcc tgt agt aat tca ggg aaa 96Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Ser Asn Ser Gly Lys 20 25 30ggt ggg gat tct gca tct act aat cct gct gac gag tct gcg aaa ggg 144Gly Gly Asp Ser Ala Ser Thr Asn Pro Ala Asp Glu Ser Ala Lys Gly 35 40 45cct aat ctt aca gaa ata agc aaa aaa att aca gat tct aat gca ttt 192Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe 50 55 60gta ctt gct gtt aaa gaa gtt gag act ttg gtt tta tct ata gat gaa 240Val Leu Ala Val Lys Glu Val Glu Thr Leu Val Leu Ser Ile Asp Glu 65 70 75 80ctt gct aag aaa gct att ggt caa aaa ata gac aat aat aat ggt tta 288Leu Ala Lys Lys Ala Ile Gly Gln Lys Ile Asp Asn Asn Asn Gly Leu 85 90 95gct gct tta aat aat cag aat gga tcg ttg tta gca gga gcc tat gca 336Ala Ala Leu Asn Asn Gln Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala 100 105 110ata tca acc cta ata aca gaa aaa ttg agt aaa ttg aaa aat tta gaa 384Ile Ser Thr Leu Ile Thr Glu Lys Leu Ser Lys Leu Lys Asn Leu Glu 115 120 125gaa tta aag aca gaa att gca aag gct aag aaa tgt tcc gaa gaa ttt 432Glu Leu Lys Thr Glu Ile Ala Lys Ala Lys Lys Cys Ser Glu Glu Phe 130 135 140act aat aaa cta aaa agt ggt cat gca gat ctt ggc aaa cag gat gct 480Thr Asn Lys Leu Lys Ser Gly His Ala Asp Leu Gly Lys Gln Asp Ala145 150 155 160acc gat gat cat gca aaa gca gct att tta aaa aca cat gca act acc 528Thr Asp Asp His Ala Lys Ala Ala Ile Leu Lys Thr His Ala Thr Thr 165 170 175gat aaa ggt gct aaa gaa ttt aaa gat tta ttt gaa tca gta gaa ggt 576Asp Lys Gly Ala Lys Glu Phe Lys Asp Leu Phe Glu Ser Val Glu Gly 180 185 190ttg tta aaa gca gct caa gta gca cta act aat tca gtt aaa gaa ctt 624Leu Leu Lys Ala Ala Gln Val Ala Leu Thr Asn Ser Val Lys Glu Leu 195 200 205aca agt cct gtt gta gca gaa agt cca aaa aaa cct cat atg gct aat 672Thr Ser Pro Val Val Ala Glu Ser Pro Lys Lys Pro His Met Ala Asn 210 215 220aat tca ggt ggg gat tct gca tct act aat cct gat gag tct gca aaa 720Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys225 230 235 240gga cct aat ctt acc gta ata agc aaa aaa att aca gat tct aat gca 768Gly Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala 245 250 255ttt tta ctg gct gtg aaa gaa gtt gag gct ttg ctt tca tct ata gat 816Phe Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp 260 265 270gaa ctt tct aaa gct att ggt aaa aaa ata aaa aat gat ggt act tta 864Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu 275 280 285gat aac gaa gca aat cga aac gaa tca ttg ata gca gga gct tat gaa 912Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu 290 295 300ata tca aaa cta ata aca caa aaa tta agt gta ttg aat tca gaa gaa 960Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu305 310 315 320tta aag aaa aaa att aaa gag gct aag gat tgt tcc caa aaa ttt act 1008Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr 325 330 335act aag cta aaa gat agt cat gca gag ctt ggt ata caa agc gtt cag 1056Thr Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln 340 345 350gat gat aat gca aaa aaa gct att tta aaa aca cat gga act aaa gac 1104Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp 355 360 365aag ggt gct aaa gaa ctt gaa gag tta ttt aaa tca cta gaa agc ttg 1152Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu 370 375 380tca aaa gca gcg caa gca gca tta act aat tca gtt aaa gag ctt aca 1200Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr385 390 395 400aat cct gtt gtg gca gaa agt cca aaa aaa cct taa 1236Asn Pro Val Val Ala Glu Ser Pro Lys Lys Pro * 405 41084411PRTospC Chimera 84Met Arg Leu Leu Ile Gly Phe Ala Leu Ala Leu Ala Leu Ile Gly Cys 1 5 10 15Ala Gln Lys Gly Ala Glu Ser Ile Gly Ser Cys Ser Asn Ser Gly Lys 20 25 30Gly Gly Asp Ser Ala Ser Thr Asn Pro Ala Asp Glu Ser Ala Lys Gly 35 40 45Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala Phe 50 55 60Val Leu Ala Val Lys Glu Val Glu Thr Leu Val Leu Ser Ile Asp Glu65 70 75 80Leu Ala Lys Lys Ala Ile Gly Gln Lys Ile Asp Asn Asn Asn Gly Leu 85 90 95Ala Ala Leu Asn Asn Gln Asn Gly Ser Leu Leu Ala Gly Ala Tyr Ala 100 105 110Ile Ser Thr Leu Ile Thr Glu Lys Leu Ser Lys Leu Lys Asn Leu Glu 115 120 125Glu Leu Lys Thr Glu Ile Ala Lys Ala Lys Lys Cys Ser Glu Glu Phe 130 135 140Thr Asn Lys Leu Lys Ser Gly His Ala Asp Leu Gly Lys Gln Asp Ala145 150 155 160Thr Asp Asp His Ala Lys Ala Ala Ile Leu Lys Thr His Ala Thr Thr

165 170 175Asp Lys Gly Ala Lys Glu Phe Lys Asp Leu Phe Glu Ser Val Glu Gly 180 185 190Leu Leu Lys Ala Ala Gln Val Ala Leu Thr Asn Ser Val Lys Glu Leu 195 200 205Thr Ser Pro Val Val Ala Glu Ser Pro Lys Lys Pro His Met Ala Asn 210 215 220Asn Ser Gly Gly Asp Ser Ala Ser Thr Asn Pro Asp Glu Ser Ala Lys225 230 235 240Gly Pro Asn Leu Thr Val Ile Ser Lys Lys Ile Thr Asp Ser Asn Ala 245 250 255Phe Leu Leu Ala Val Lys Glu Val Glu Ala Leu Leu Ser Ser Ile Asp 260 265 270Glu Leu Ser Lys Ala Ile Gly Lys Lys Ile Lys Asn Asp Gly Thr Leu 275 280 285Asp Asn Glu Ala Asn Arg Asn Glu Ser Leu Ile Ala Gly Ala Tyr Glu 290 295 300Ile Ser Lys Leu Ile Thr Gln Lys Leu Ser Val Leu Asn Ser Glu Glu305 310 315 320Leu Lys Lys Lys Ile Lys Glu Ala Lys Asp Cys Ser Gln Lys Phe Thr 325 330 335Thr Lys Leu Lys Asp Ser His Ala Glu Leu Gly Ile Gln Ser Val Gln 340 345 350Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr His Gly Thr Lys Asp 355 360 365Lys Gly Ala Lys Glu Leu Glu Glu Leu Phe Lys Ser Leu Glu Ser Leu 370 375 380Ser Lys Ala Ala Gln Ala Ala Leu Thr Asn Ser Val Lys Glu Leu Thr385 390 395 400Asn Pro Val Val Ala Glu Ser Pro Lys Lys Pro 405 41085192PRTborrelia burgdorferi 85Cys Asn Asn Ser Gly Lys Asp Gly Asn Thr Ser Ala Asn Ser Ala Asp 1 5 10 15Glu Ser Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr 20 25 30Glu Ser Asn Ala Val Val Leu Ala Val Lys Glu Val Glu Thr Leu Leu 35 40 45Thr Ser Ile Asp Glu Leu Ala Lys Ala Ile Gly Lys Lys Ile Lys Asn 50 55 60Asp Val Ser Leu Asp Asn Glu Ala Asp His Asn Gly Ser Leu Ile Ser65 70 75 80Gly Ala Tyr Leu Ile Ser Thr Leu Ile Thr Lys Lys Ile Ser Ala Ile 85 90 95Lys Asp Ser Gly Glu Leu Lys Ala Glu Ile Glu Lys Ala Lys Lys Cys 100 105 110Ser Glu Glu Phe Thr Ala Lys Leu Lys Gly Glu His Thr Asp Leu Gly 115 120 125Lys Glu Gly Val Thr Asp Asp Asn Ala Lys Lys Ala Ile Leu Lys Thr 130 135 140Asn Asn Asp Lys Thr Lys Gly Ala Asp Glu Leu Glu Lys Leu Phe Glu145 150 155 160Ser Val Lys Asn Leu Ser Lys Ala Ala Lys Glu Met Leu Thr Asn Ser 165 170 175Val Lys Glu Leu Thr Ser Pro Val Val Ala Glu Ser Pro Lys Lys Pro 180 185 19086191PRTborrelia burgdorferi 86Asn Ser Gly Lys Gly Gly Asn Thr Ser Ala Asn Ser Ala Asp Glu Ser 1 5 10 15Val Lys Gly Pro Asn Leu Thr Glu Ile Ser Lys Lys Ile Thr Glu Ser 20 25 30Asn Ala Val Val Leu Ala Val Lys Glu Ile Glu Thr Leu Leu Ala Ser 35 40 45Ile Asp Glu Leu Ala Thr Lys Ala Ile Gly Lys Lys Ile Gln Gln Asn 50 55 60Gly Gly Leu Ala Val Glu Ala Gly His Asn Gly Thr Leu Leu Ala Gly65 70 75 80Ala Tyr Thr Ile Ser Lys Leu Ile Thr Gln Lys Leu Asp Gly Leu Lys 85 90 95Asn Ser Glu Lys Leu Lys Glu Lys Ile Glu Asn Ala Lys Lys Cys Ser 100 105 110Glu Asp Phe Thr Lys Lys Leu Glu Gly Glu His Ala Gln Leu Gly Ile 115 120 125Glu Asn Val Thr Asp Glu Asn Ala Lys Lys Ala Ile Leu Ile Thr Asp 130 135 140Ala Ala Lys Asp Lys Gly Ala Ala Glu Leu Glu Lys Leu Phe Lys Ala145 150 155 160Val Glu Asn Leu Ala Lys Ala Ala Lys Glu Met Leu Ala Asn Ser Val 165 170 175Lys Glu Leu Thr Ser Pro Ile Val Ala Glu Ser Pro Lys Lys Pro 180 185 190