MUTANT FRAGMENTS OF OSPA AND METHODS AND USES RELATING THERETO

Abstract

The present invention relates to a polypeptide comprising a mutant fragment of an outer surface protein A (OspA), a nucleic acid coding the same, a pharmaceutical composition (particularly for use as a medicament of in a method of treating or preventing a Borrelia infection) comprising the polypeptide and/or the nucleic acid, a method of treating or preventing a Borrelia infection and a method of immunizing a subject.

Claims

1.-19. (canceled)

20. A method for producing a polypeptide comprising a mutant fragment of an outer surface protein A (OspA), wherein the mutant OspA fragment is defined by SEQ ID NO: 216, or a functional variant thereof, the method comprising the following steps: a) introducing a vector encoding the polypeptide into a host cell, b) growing the host cell under conditions allowing for expression of said polypeptide, c) homogenizing said host cell, and d) subjecting the host cell homogenate to purification steps.

21. The method according to claim 20, wherein said functional variant has at least 95% sequence identity to the wild-type OspA fragment.

22. The method according to claim 20, wherein the polypeptide comprises a heterodimer selected from the group consisting of Lip-S1D1-S2D1 (SEQ ID NO: 186), Lip-S2D1-S1D1 (SEQ ID NO: 192), Lip-S1D1-S2D4 (SEQ ID NO: 198) and Lip-S2D4-S1D1 (SEQ ID NO: 203).

23. The method according to claim 20, wherein the polypeptide consists of a heterodimer selected from the group consisting of Lip-S1D1-S2D1 (SEQ ID NO: 186), Lip-S2D1-S1D1 (SEQ ID NO: 192), Lip-S1D1-S2D4 (SEQ ID NO: 198) and Lip-S2D4-S1D1 (SEQ ID NO: 203).

24. The method according to claim 20, wherein the vector comprises a nucleic acid molecule encoding said polypeptide.

25. The method according to claim 24, wherein said nucleic acid molecule encoding said polypeptide is defined by SEQ ID NO: 48.

26. The method according to claim 20, wherein said vector is pET28b(+).

27. The method according to claim 20, wherein said host cell is E. coli.

28. The method according to claim 27, wherein said E. coli is an E. coli BL21 or an E. coli BL21 Star cell.

29. The method according to claim 20, wherein said purification steps comprise enriching the polypeptide in the lipid phase by phase separation and purifying over a gel filtration column.

30. The method according to claim 29, wherein said purification steps further comprise processing over a buffer exchange column.

31. A method for producing a pharmaceutical composition comprising a polypeptide comprising a mutant fragment of an outer surface protein A (OspA), wherein the mutant OspA fragment is defined by SEQ ID NO: 216, or a functional variant thereof, the method comprising combining said polypeptide with one or more pharmaceutically acceptable carriers or excipients.

32. The method according to claim 31, wherein said functional variant has at least 95% sequence identity to the wild-type OspA fragment.

33. The method according to claim 31, wherein said polypeptide comprises a heterodimer selected from the group consisting of Lip-S1D1-S2D1 (SEQ ID NO: 186), Lip-S2D1-S1D1 (SEQ ID NO: 192), Lip-S1D1-S2D4 (SEQ ID NO: 198) and Lip-S2D4-S1D1 (SEQ ID NO: 203).

34. The method according to claim 31, wherein said polypeptide consists of a heterodimer selected from the group consisting of Lip-S1D1-S2D1 (SEQ ID NO: 186), Lip-S2D1-S1D1 (SEQ ID NO: 192), Lip-S1D1-S2D4 (SEQ ID NO: 198) and Lip-S2D4-S1D1 (SEQ ID NO: 203).

35. The method according to claim 31, wherein said pharmaceutical composition comprises Lip-S1D1-S2D1 (SEQ ID NO: 186) and Lip-S5D1-S6D1 (SEQ ID NO: 190).

36. The method according to claim 31, wherein said one or more pharmaceutically acceptable carriers or excipients are selected from the group comprising saline, buffered saline, dextrose, water, glycerol, ethanol and adjuvants.

37. The method according to claim 36, wherein said buffered saline is phosphate buffered saline.

38. The method according to claim 36, wherein said adjuvant is aluminium hydroxide.

39. The method according to claim 31, wherein said pharmaceutical composition is a vaccine.

Description

[0250] In connection with the present invention

[0251] FIGS. 1A-1C schematically shows the production of mutant OspA fragment heterodimers according to the current invention.

[0252] FIG. 2 schematically represents the polypeptide components of one possible pharmaceutical composition of the current invention comprising three different mutant OspA heterodimers.

[0253] FIG. 3 shows the chemical structure of Pam.sub.3Cys, an example of a fatty acid substituted cysteine, such as would be found at the N-terminus of lipidated polypeptides of the current invention.

[0254] Table 1 shows the thermal stability of the folding of mutant serotype 2 OspA fragments with disulfide bond types from D1 to D5 (see Table A-4) compared to the wild-type serotype 2 OspA fragment without disulfide bonds (D0).

[0255] Table 2 shows the protection of mice from B. afzelii infection by the Tick Challenge Method following immunization with mutant serotype 2 OspA fragments with disulfide bond types D1 to D5, including control groups of mice immunized with PBS, full-length OspA or the wild-type serotype 2 OspA fragment.

[0256] Table 3 shows the protection of mice from B. afzelii infection by the Tick Challenge Method following immunization with lipidated mutant serotype 2 OspA fragments with disulfide bond types D2, D3 and D4, including control groups of mice immunized with PBS or full-length OspA protein.

[0257] Table 4 shows the protection of mice from B. burgdorferi s.s. delivered by needle challenge or from B. afzelii delivered by tick challenge by immunization with lipidated His-tagged mutant OspA serotype 1/serotype 2 fragment heterodimer (Lip-S1D1-S2D1-His). Control groups included mice immunized with lipidated His-tagged mutant OspA serotype 1 (Lip-M1B-His) or serotype 2 (Lip-M2B-His) fragment monomers individually or with adjuvant alone.

[0258] The figures and tables which may be referred to in the specification are described below in more detail.

[0259] FIGS. 1A-1C Production of a mutant OspA heterodimer of the invention comprising mutant OspA C-terminal fragments from two different serotypes of Borrelia sp. (FIG. 1A) Schematic representation of a nucleic acid encoding a lipidated mutant OspA heterodimer. The components, from 5 to 3 comprise the coding sequences for a lipidation signal sequence (Lip signal), a small cysteine-containing peptide for N-terminal lipidation (Lipidation peptide=LP), a mutant C-terminal fragment of OspA with two non-native cysteines, a short linker peptide, LN1, followed by a second mutant OspA C-terminal fragment with two non-native cysteines. (FIG. 1B) The intermediate mutant OspA heterodimer polypeptide comprises the nascent product directly following translation of the nucleic acid construct. From the N- to the C-terminus, this polypeptide consists of a lipidation signal sequence (Lip signal), a cysteine-containing peptide for lipidation (LP), a mutant OspA fragment with a non-native disulfide bond, a short linker peptide, LN1, followed by a second mutant OspA fragment with a non-native disulfide bond. (FIG. 1C) The final lipidated mutant OspA heterodimer polypeptide after post-translational modification. The heterodimer, from the N- to the C-terminus, consists of a short cysteine-containing peptide with the N-terminal cysteine lipidated (indicated by Lip), a mutant OspA fragment stabilized by a disulfide bond, a linker peptide, LN1, and a second mutant OspA fragment stabilized by a disulfide bond. The lipidation signal sequence is cleaved off during post-translational modification of the polypeptide as shown.

[0260] FIG. 2 An example of a preferred pharmaceutical composition according to the current invention. Three mutant OspA heterodimers, each comprising mutated OspA fragments from two different Borrelia serotypes are present in the composition, together providing OspA antigens from six different Borrelia serotypes. Such a pharmaceutical composition enables simultaneous immunization against six of the most prevalent serotypes of Borrelia.

[0261] FIG. 3 Diagram of the chemical structure of Pam.sub.3Cys, an example of a fatty acid substitution of the N-terminal cysteine of full-length wild-type OspA protein as well as of lipidated mutant OspA fragment monomers and heterodimers of the invention. During post-translational modification of a full-length OspA protein or polypeptides of the invention, the N-terminal lipidation signal sequence is cleaved off and fatty acids, most commonly three palmitoyl moieties (Pam.sub.3), are enzymatically covalently attached to the N-terminal cysteine residue (the S atom of which is indicated by an arrow). The remaining residues of the polypeptide chain, which are located C-terminally from the Pam.sub.3Cys residue, are represented by Xn. (Modified from Bouchon, et al. (1997) Analytical Biochemistry 246: 52-61.)

TABLE-US-00007 TABLE 1 Thermal stability of non-lipidated, His-tagged B. afzelii K78 mutant serotype 2 OspA fragments with different placement of disulfide bonds. Mutant serotype 2 OspA fragments with different cysteine bond types (see Table A-4) were solubilized in 50 mM Tris-HCl, 150 mM NaCl (pH 8.0) and tested for thermal stability compared with the wild-type serotype 2 OspA fragment (S2D0). The presence of a disulfide bond resulted in an increased melting temperature compared to the wild-type serotype 2 OspA fragment. Serotype 2 OspA mutant Melting temperature fragment SEQ ID NO: ( C.) S2D0-His* 1 47.6 S2D1-His 2 70.4 S2D2-His 3 54.6 S2D3-His 4 58.6 S2D4-His 5 58.4 S2D5-His 6 53.8 *see Tables A-4 and A-5 for nomenclature.

TABLE-US-00008 TABLE 2 Protection of mice from B. afzelii infection by the tick challenge method by immunization with non-lipidated mutant serotype 2 OspA fragments. Five non-lipidated mutant serotype 2 OspA fragments were tested for protective capacity at two different doses (30 g and 5 g) and compared with the wild-type serotype 2 fragment. Groups of mice immunized with adjuvant alone or with non-lipidated full-length serotype 2 OspA served as negative and positive controls, respectively. All antigens were His-tagged and non-lipidated. The data presented combine the results of several experiments performed under identical conditions. 3 30 g 3 5 g (data from 11 experiments) (data from 4 experiments) (all groups include Al(OH).sub.3) (all groups include Al(OH).sub.3) Infected Infected Immunogen mice total mice p-value mice total mice p-value Adjuvant alone 67 73 n/a 20 23 n/a Full-length OspA K78- 15 87 <0.001*** 0 25 <0.001*** His (SEQ ID NO: 209) S2D0-His 20 27 0.045* 5 16 0.001*** (SEQ ID NO: 1) S2D1-His 7 32 <0.001*** 1 25 <0.001*** (SEQ ID NO: 2) S2D2-His 2 29 <0.001*** 3 26 <0.001*** (SEQ ID NO: 3) S2D3-His 10 44 <0.001*** 0 21 <0.001*** (SEQ ID NO: 4) S2D4-His 6 35 <0.001*** 3 27 <0.001*** (SEQ ID NO: 5) S2D5-His 6 37 <0.001*** 2 11 <0.001*** (SEQ ID NO: 6) *significant (0.05), ** highly significant (0.01), ***extremely significant (0.001), Fisher's exact test, two-tailed.

TABLE-US-00009 TABLE 3 Protection of mice from B. afzelii infection by the Tick Challenge Method by immunization with decreasing doses of lipidated mutant serotype 2 OspA fragments. Three lipidated mutant serotype 2 OspA fragments with different disulfide bond types were tested for protective capacity. Groups of mice immunized with adjuvant alone or with non- lipidated full-length serotype 2 OspA served as negative and positive controls, respectively. All antigens were His-tagged. 3 3 g 3 1 g 3 0.3 g (data from 3 experiments) (data from 5 experiments) (data from 4 experiments) (all groups included Al(OH).sub.3) (all groups included Al(OH).sub.3) (all groups included Al(OH).sub.3) Infected Infected Infected Immunogen mice Total mice p-value mice Total mice p-value mice Total mice p-value Adjuvant 22 24 n/a 33 37 n/a 28 30 n/a alone Full-length 0 14 <0.001*** 0 21 <0.001*** n/a n/a n/a OspA K78- His (SEQ ID NO: 209) Lip-S2D2- 0 17 <0.001*** 0 15 <0.001*** 0 21 <0.001*** His (SEQ ID NO: 142) Lip-S2D3- 1 15 <0.001*** 1 12 <0.001*** 5 19 <0.001*** His (SEQ ID NO: 143) Lip-S2D4- 0 8 <0.001*** 0 14 <0.001*** 0 19 <0.001*** His (SEQ ID NO: 144) * significant (<0.05), ** highly significant (<0.01), ***extremely significant (0.001), Fisher's exact test, two-tailed.

TABLE-US-00010 TABLE 4 Protection of mice from Borrelia infection by both needle challenge (B. burgdorferi s.s.) and Tick Challenge Method (B. afzelii) by immunization with lapidated His-tagged mutant serotype1/serotype 2 OspA fragment heterodimers. The lipidated His-tagged mutant serotype 1/serotype 2 OspA fragment heterodimer protein (Lip-S1D1-S2D1-His) was tested for protective capacity. Groups of mice immunized three times at two week intervals with adjuvant alone or with lipidated His-tagged mutant serotype 1 (Lip-S1D1-His) or serotype 2 (Lip-S2D1-His) OspA fragment monomers individually served as negative and positive controls, respectively. Immunized mice were challenged two weeks after the last immunization with either B. burgdorferi s.s. via needle challenge (Experiments 1-3) or with B. afzelii via infected ticks (Experiments 4-6). All antigens were lipidated and His-tagged. Needle challenge Infected/ Infected/ Infected/ (serotype 1: Total Total Total Immunogen Dose B. burgdorferi s.s.) Exp. 1 Exp. 2 Exp. 3 Lip-S1D1-S2D1- 3 5.0 N40 (ST1) 0/10*** 0/9*** 4/10** Lip-S1D1-His 3 2.5 N40 (ST1) 2/10*** 1/10* 4/10** Lip-S2D1-His 3 2.5 N40 (ST1) 1/10*** 3/10 5/10* Adjuvant alone N40 (ST1) 10/10 8/10 10/10 Tick challenge (Serotype 2: B. afzelii) Exp. 4 Exp. 5 Exp. 6 Lip-S1D1-S2D1- 3 2.0 Tick (ST2) 0/10*** 0/9*** 0/6*** Lip-S1D1-His 3 1.0 Tick (ST2) 2/10*** 2/8** 2/4 Lip-S2D1-His 3 1.0 Tick (ST2) 1/8*** 0/4** 0/4** Adjuvant alone Tick (ST2) 9/9 8/8 7/7 P-value; Fisher's exact test, two tailed. *significant (<0.05), **highly significant (<0.01), ***extremely significant (<0.001) indicates data missing or illegible when filed

Examples

Example 1. Assessment of Thermal Stability of Mutant Serotype 2 OspA Fragments

[0262] Experimental Procedures

[0263] Thermal Stability

[0264] The melting temperatures (T.sub.m) of non-lipidated mutant serotype 2 OspA fragment monomers were determined by the fluorescence-based thermal shift assay described by Pantoliano, et al. (J. Biomol Screen 6:429-440 (2001)). The fluorescent dye SYPRO Orange protein gel stain (supplied as a 5000 concentrate in DMSO by Sigma, U.S.A) was used to monitor protein unfolding. In each well, 7.5 l of SYPRO Orange (diluted 1:1000 from the stock solution) and 17.5 l of a solution of protein (1 g or 2 g) in buffer were combined. The protein samples were heated from 25 C. to 95 C. at a rate of 0.2 C./10 sec in the CFX96 Real-time Detection System (Bio-Rad, USA) and fluorescent changes were monitored. Fluorescence intensity was measured with excitation and emission wavelengths of 490 and 575 nm, respectively. The Tm was determined using the Bio-Rad CFX Manager 2.0 program. The Tm values of non-lipidated His-tagged serotype 2 OspA mutant fragments were measured in four different buffer systems: 50 mM Tris-HCl, 150 mM NaCl (pH 9.0); 50 mM Tris-HCl, 150 mM NaCl (pH 8.0); PBS (pH 7.4); and 25 mM HEPES, 150 mM NaCl (pH 6.5), using the non-lipidated serotype 2 OspA wild-type fragment (52D0) as a control.

[0265] Results

[0266] In all cases, mutant serotype 2 OspA fragments with an introduced cysteine bond had higher melting temperatures than the wild-type serotype 2 OspA fragment (S2D0) (see Table 1). The melting temperatures were tested in four different buffer systems with similar results (data for proteins dissolved in 50 mM Tris-HCl, 150 mM NaCl (pH 8.0) is shown in Table 1), indicating that the stability of the proteins is similar over a wide pH range. This result lends credence to the hypothesis that the introduced disulfide bond stabilizes the OspA fragment.

Example 2. Protection of Mice from Infection with B. afzelii in the Tick Challenge Method by Immunization with Non-Lipidated his-Tagged Mutant Serotype 2 OspA Fragment Monomers

[0267] Experimental Procedures

[0268] Cloning and Expression of Recombinant Proteins

[0269] The wild-type serotype 2 OspA fragment as well as the serotype 2 mutant OspA fragments with cysteine bond types 1-5 (SEQ ID NOs: 1, 2, 3, 4, 5 and 6, respectively), were codon-optimized for E. coli expression by GenScript, USA. The non-lipidated serotype 2 mutant OspA fragments were C-terminally histidine-tagged for purification purposes. Gene fragments were cloned into the pET28b(+) vector (Novagen, USA), a vector containing a Kanamycin resistance cassette as well as a T7 promoter. The monomers were expressed in BL21 Star(DE3) cells (Invitrogen, USA) at 37 C. by the addition of IPTG. Cells were collected after 4 h by centrifugation and the pellet was stored at 70 C. for up to 12 months prior to further processing.

[0270] Purification of Non-Lipidated his-Tagged Wild-Type and Mutant OspA Fragment Monomer Proteins

[0271] Cells were disrupted mechanically by high-pressure homogenization and the soluble fraction containing the His-tagged OspA fragments was applied to a Ni-sepharose column (Ni Sepharose 6 Fast Flow; GE Healthcare, United Kingdom) and the His-tagged OspA fragments were eluted on an Imidazole gradient (0-250 mM). Pooled fractions were further purified over a gel filtration column (Superdex 200, GE Healthcare) followed by a buffer exchange column (Sephadex G-25, GE Healthcare). His-tagged OspA fragment peaks were pooled on the basis of the analytical size exclusion column and reversed phase chromatography. After sterile filtration, the purified proteins were stored at 20 C. until formulation.

[0272] Immunization of Mice

[0273] Female C3H/HeN (H-2.sup.k) mice were used for all studies (Harlan, Italy). Prior to each challenge, groups of five 8-week-old mice were bled via the tail vein and pre-immune sera were prepared and pooled. Five non-lipidated mutant serotype 2 OspA fragment proteins (S2D1-5, SEQ ID NOs: 2, 3, 4, 5 and 6, respectively), were tested in fifteen separate experiments. Three subcutaneous (s c) immunizations of 100 L, were administered at two week intervals. Doses used were 30 and 5 g of the respective protein, tested in 11 and 4 experiments respectively. All formulations included aluminium hydroxide (Al(OH).sub.3) at a final concentration of 0.15%. One week after the third immunization, blood was collected and hyper-immune sera were prepared. In each experiment, one group injected with PBS formulated with Al(OH).sub.3 was included as a negative control and one group of mice was immunized with S2D0, the wild-type C-terminal OspA fragment from B. afzelii strain K78 (SEQ ID NO: 1). Another group immunized with a non-lipidated full-length wild-type OspA protein from B. afzelii, strain K78 (SEQ ID NO: 209), also formulated with 0.15% Al(OH).sub.3, was included as positive control in each animal study. All animal experiments were conducted in accordance with Austrian law (BGB1 Nr. 501/1989) and approved by Magistratsabteilung 58.

[0274] Tick Challenge of Immunized Mice and Collection of Sera and Tissues (Herein Referred to Also as Tick Challenge Method)

[0275] Tick challenge of immunized mice was done two weeks after the last immunization. In order to challenge the immunized mice with B. afzelii, the hair of the back of each mouse was removed with Veet Cream (Reckitt Benckiser, United Kingdom) and a small ventilated container was glued to the skin with super glue (Pattex, Germany). Thereafter, one or two I. ricinus nymphs infected with B. afzelii, strain IS1, were applied per mouse, allowed to attach and feed to depletion. The feeding status was monitored for each individual tick and only mice where at least one fully-fed tick was collected were included in the final readout. No distinction was made between mice where one or two fully-fed ticks were collected.

[0276] Six weeks after the tick application, blood was collected by orbital bleeding and final sera were prepared and used for VlsE ELISA analysis to determine infection status. The mice were then sacrificed by cervical dislocation and one ear from each mouse was collected, DNA extracted and subjected to nested PCR analysis to identify Borrelia in tissue.

[0277] Infection Readout

[0278] Only mice where the applied tick(s) fed to completion and could be collected were included in the final readout of the experiment. The mice were sacrificed 6 weeks after tick application and organs as well as final sera were collected. The final infection readout was based on two different analyses (nested PCR targeting the 16S-23S intergenic spacer and VlsE (IR6) ELISA as described in detail below).

[0279] Nested PCR Targeting the 16S-23S Intergenic Spacer

[0280] One ear from each mouse was subjected to DNA extraction and purification using the DNeasy Blood and Tissue Kit (Qiagen, Germany) according to the manufacturer's instructions, with the following modification. Each ear was digested over night at 60 C. in recombinant Proteinase K, PCR grade (Roche, 14-22 mg/mL). The DNA was eluted in 50 L deionized sterile water and stored at 20 C. until further analysis. As a negative control, one empty purification column was included in each DNA extraction and purification and the eluate subjected to nested PCR. All DNA extracts were screened for the presence of Borrelia DNA by a nested PCR procedure, comprising 40 cycles of 94 C. for 30 s, 56 C. for 30 s and 72 C. for 60 s using the primers; Forward 5-GTATGTTTAGTGAGGGGGGTG-3 (SEQ ID NO: 26) and Reverse 5-GGATCATAGCTCAGGTGGTTAG-3 (SEQ ID NO: 27). From the reaction volume of 10 L, 1 L was used as template for the nested PCR reaction. The nested PCR step comprised 25 cycles of 94 C. for 30 s, 60 C. for 30 s and 72 C. for 60 s using the primers; Forward nested 5-AGGGGGGTGAAGTCGTAACAAG-3 (SEQ ID NO: 28) and Reversed nested 5-GTCTGATAAACCTGAGGTCGGA-3 (SEQ ID NO: 29). Of the final reaction volume, 5 L was separated on a 1% agarose gel containing ethidium bromide and bands were visualized in UV-light.

[0281] In each PCR analysis, DNA purified from an in vitro grown culture of B. afzelii strain K78 was used as a positive control template. In addition, PBS was used instead of extracted DNA as negative control. Five microliters of the final product was separated on a 1% agarose gel containing ethidium bromide and bands were visualized in UV-light.

[0282] ELISA with the Invariable Region 6 (IR6) of the Variable Major Protein-Like Sequence E Protein (VlsE)

[0283] A biotinylated 25-mer peptide (MKKDDQIAAAMVLRGMAKDGQFALK) (SEQ ID NO: 30) derived from the sequence of B. garinii strain IP90 was used for analysis (Liang F T, et al. (1999) J Immunol. 163:5566-73). Streptavidin pre-coated 96-well ELISA plates (Nunc, Denmark) were coated with 100 L/well (1 g/mL) biotinylated peptide in PBS supplemented with 0.1% Tween 20 (PBS/0.1T). The plates were incubated overnight at 4 C. After coating with the peptide, the plates were washed once with PBS/0.1T. The plates were then blocked for one hour at room temperature (RT) with 100 L/well of PBS+2% BSA, before being washed again with PBS/0.1T. Reactivity of post-challenge sera to the peptide was tested at 1:200, 1:400 and 1:800 dilutions in PBS+1% BSA. Plates were incubated for 90 min at RT before being washed three times with PBS/0.1T. Each well then received 50 L of 1.3 g/mL polyclonal rabbit anti-mouse IgG conjugated to HRP (Dako, Denmark) in PBS+1% BSA. The plates were then incubated for 1 h at RT. After three washes with PBS/0.1T, ABTS (50 l/well) was added as substrate (Sigma-Aldrich, USA) and color was allowed to develop for 30 min. Absorbance was measured at 405 nm. All sera were tested in duplicate; negative controls included PBS instead of sera, as well as plates not coated with the peptide. Sera from mice shown to be culture positive for B. afzelii infection were used as positive controls.

[0284] Results

[0285] Levels of Protection in the Tick Challenge Method

[0286] Extremely significant levels of protection (p-value 0.001) were seen for all five stabilized OspA B. afzelii fragments at both of the doses tested (30 g and 5 g, see Table 2). The high infection rates in the PBS control group indicate that the ticks were infected with high frequency. Additionally, the positive control, non-lipidated full-length OspA from B. afzelii strain K78, was very protective. Together these control groups indicate the high reliability of the experimental readout.

[0287] Protection data from the seven experiments are combined and summarized in Table 2. The two methods employed to verify infection, namely ELISA and PCR, gave virtually identical results (not shown), demonstrating the robustness of these methods for assessment of infection in the tick challenge method.

Example 3. Protection of Mice from Infection with B. afzelii by the Tick Challenge Method by Immunization with Lipidated Mutant Serotype 2 OspA Fragments

[0288] Experimental Procedures

[0289] Cloning and Expression of Lipidated his-Tagged Mutant OspA Fragment Proteins

[0290] The serotype 2 mutant OspA fragments with cysteine bond types 2, 3 and 4 (SEQ ID NOs: 142, 143 and 144, respectively) were modified by the addition of a lipidation signal sequence derived from OspA (SEQ ID NO: 14) and followed directly C-terminally by a CKQN peptide (SEQ ID NO: 211) to provide an N-terminal cysteine for lipidation. All mutant OspA fragments were C-terminally histidine-tagged for purification purposes. Gene fragments were cloned into the pET28b(+) vector (Novagen), a vector containing a Kanamycin resistance cassette as well as a T7 promoter. The lipidated monomers were expressed in BL21 Star(DE3) cells (Invitrogen) and after induction by IPTG, the growth temperature of the cells was lowered from 37 C. to 25 C. to promote efficient post-translational processing of the proteins. Cells were collected after 4 h by centrifugation and the pellet was stored at 70 C. for up to 12 months prior to further processing.

[0291] Purification of Lipidated his-Tagged Wild-Type and Mutant OspA Fragment Monomer Proteins

[0292] Cells were disrupted mechanically by high-pressure homogenization and the lipidated His-tagged OspA fragment monomer polypeptides were enriched in the lipid phase by phase separation, using Triton X-114 as detergent. Subsequently, the diluted detergent phase (20 to 30 fold) was applied to a Ni-sepharose column (Ni Sepharose 6 Fast Flow; GE Healthcare) and the lipidated His-tagged OspA fragments were eluted by Imidazole gradient (0-250 mM) elution. Pooled fractions were further purified over a gel filtration column (Superdex 200, GE Healthcare) followed by a buffer exchange column (Sephadex G-25, GE Healthcare). Lipidated His-tagged OspA fragment peaks were pooled on the basis of the analytical size exclusion column and reversed phase chromatography. After sterile filtration, the purified proteins were stored at 20 C. until formulation.

[0293] Immunization of Mice

[0294] Three lipidated mutant OspA proteins (Lip-S2D2-His, Lip-S2D3-His and Lip-S2D4-His) were expressed and purified as described above. In vivo protection studies were performed also as above using PBS and non-lipidated full-length serotype 2 OspA as negative and positive controls, respectively. All immunogens were formulated with 0.15% Al(OH).sub.3. Mice were injected subcutaneously three times at two week intervals with formulations containing 3.0 g, 1.0 g or 0.3 g antigen and challenged with infected ticks two weeks after the last immunization. Mice were sacrificed six weeks following tick challenge and infection was assessed.

[0295] Results

[0296] Levels of Protection in the Tick Challenge Method

[0297] All three lipidated mutant OspA fragments conferred extremely significant levels of protection (p-value0.001) from B. afzelii challenge even at the lowest tested dose (Table 3). Infection rates in the PBS groups were high, indicating that the ticks were infected to a high frequency. The positive control antigen, full-length non-lipidated OspA from B. afzelii strain K78, was also very protective. Together, these control groups indicate the high reliability of the method of infection and thus give high credibility to the results observed following immunization with the lipidated mutant OspA fragments.

Example 4. Protection of Mice from Borrelia Infection by Immunization with Lipidated his-Tagged Mutant OspA Fragment Heterodimers of Different Serotypes

[0298] Experimental Procedures

[0299] Cloning and Expression of Lipidated his-Tagged Mutant OspA Fragment Heterodimers

[0300] The mutant OspA fragment monomers from B. burgdorferi s.s. strain B31, B. afzelii strain K78, B. garinii strain PBr, B. bavariensis strain PBi, B. garinii strain PHEi and B. garinii strain DK29 were codon-optimized for E. coli expression by GenScript, USA. The hLFA-1-like epitope (aa 164-174, SEQ ID NO: 17) of the OspA from B. burgdorferi s.s. strain B31 was replaced by a non-hLFA-1-like sequence NFTLEGKVAND from B. afzelii strain K78 (SEQ ID NO: 18). The lipidation signal sequence added to the mutant OspA fragment heterodimers was derived from the E. coli major outer membrane lipoprotein, Lpp, and was followed directly C-terminally by a CSS peptide (SEQ ID NO: 210) to provide an N-terminal cysteine for lipidation. The mutant OspA fragment heterodimers were generated by fusing different mutant OspA fragment monomers as described above via a 21 amino acid linker sequence, originating from two separate loop regions of the N-terminal half of OspA from B. burgdorferi s.s. strain B31 (LN1; aa 65-74 and aa 42-53 with an amino acid exchange of D53S, SEQ ID NO: 184). The heterodimers were constructed with a His-tag for purification purposes. Gene fragments were cloned into the pET28b(+) vector (Novagen), a vector containing a Kanamycin resistance cassette as well as a T7 promoter. The lipoproteins of the stabilized heterodimers were expressed in BL21 Star(DE3) cells (Invitrogen) and after induction by IPTG, the growth temperature of the cells was lowered from 37 C. to 25 C. to promote efficient post-translational processing of the proteins. Cells were collected after 4 h by centrifugation and the pellet was stored at 70 C. for up to 12 months prior to further processing.

[0301] Purification of Lipidated his-Tagged Mutant OspA Fragment Heterodimers

[0302] Cells were disrupted mechanically by high-pressure homogenization and the lipidated His-tagged mutant OspA fragment heterodimers were enriched in the lipid phase by phase separation, using Triton X-114 as detergent. Subsequently, the diluted detergent phase (20 to 30 fold) was applied to a Ni-sepharose column (Ni Sepharose 6 Fast Flow; GE Healthcare) and the lipidated His-tagged OspA heterodimers were eluted by Imidazole gradient (0-250 mM) elution. Pooled fractions were further purified over a gel filtration column (Superdex 200, GE Healthcare) followed by a buffer exchange column (Sephadex G-25, GE Healthcare). The lipidated His-tagged mutant OspA heterodimer peaks were pooled on the basis of the analytical size exclusion column and reversed phase chromatography. After sterile filtration, the purified heterodimers were stored at 20 C. until formulation.

[0303] Immunization of Mice

[0304] Female C3H/HeN mice (Janvier, France) were used for all studies. Prior to each challenge, groups of ten 8-week-old mice were bled via the facial vein and pre-immune sera were prepared and pooled. Three subcutaneous (s.c.) immunizations of 100 L each were administered at two week intervals. Each dose contained either 2 g or 5 g of the heterodimer protein Lip-S1D1-S2D1-His (SEQ ID NO: 49), or 1.0 g or 2.5 g of the respective monomer proteins, formulated with aluminium hydroxide (Al(OH).sub.3) at a final concentration of 0.15%. One week after the third immunization, blood was collected from the facial vein and hyper-immune sera were prepared. In each experiment, one group immunized with Al(OH).sub.3 alone was included as a negative control. All animal experiments were conducted in accordance with Austrian law (BGB1 Nr. 501/1989) and approved by Magistratsabteilung 58.

[0305] Tick Challenge of Immunized Mice and Collection of Sera and Tissues (Herein Referred to Also as Tick Challenge Method)

[0306] In order to challenge the immunized mice with B. afzelii, the hair of the back of each mouse was removed with Veet Cream (Reckitt Benckiser) and a small ventilated container was glued to the skin with super glue (Pattex). Thereafter, one or two I. ricinus nymphs infected with B. afzelii, strain IS1, were applied per mouse, allowed to attach and feed until they were fully engorged and dropped off. The feeding status was monitored for each individual tick and only mice from which at least one fully fed tick was collected were included in the final readout.

[0307] Needle Challenge of Immunized Mice with In Vitro Grown Borrelia

[0308] Two weeks after the last immunization, the mice were challenged s.c. with Borrelia diluted in 100 L Borrelia growth medium (BSK II). The challenge doses were strain-dependent, the virulence of the individual strains being assessed by challenge experiments for determination of ID.sub.50. Doses employed for needle challenge experiments ranged from 20 to 50 times the ID.sub.50.

[0309] Sacrifice of Mice and Collection of Material

[0310] Four weeks after needle challenge with B. burgdorferi s.s. or six weeks after tick challenge with B. afzelii, mice were sacrificed by cervical dislocation. The blood was collected by orbital bleeding and final sera were prepared and used for VlsE ELISA to determine infection status. In addition, one ear from each mouse was collected, and DNA was extracted and subjected to qPCR for identification of Borrelia. The final infection readout was based on two different analyses (qPCR targeting recA and VlsE ELISA).

[0311] ELISA with the Invariable Region 6 (IR6) of VlsE

[0312] A biotinylated 25-mer peptide (MKKDDQIAAAMVLRGMAKDGQFALK) (SEQ ID NO: 30) derived from the sequence of B. garinii strain IP90 was used for the analysis (Liang F T, Alvarez A L, Gu Y, Nowling J M, Ramamoorthy R, Philipp M T. An immunodominant conserved region within the variable domain of VlsE, the variable surface antigen of Borrelia burgdorferi. J Immunol. 1999; 163:5566-73). Streptavidin pre-coated 96-well ELISA plates (Nunc), were coated with 100 L/well (1 g/mL) peptide in PBS supplemented with 0.1% Tween (PBS/0.1T). The plates were incubated overnight at 4 C. After coating with the peptide, the plates were washed once with PBS/0.1T. The plates were then blocked for one hour at room temperature (RT) with 100 L/well of PBS+2% BSA, before being washed again with PBS/0.1T. Reactivity of post-challenge sera to the peptide was tested at 1:200, 1:400 and 1:800 dilutions in PBS+1% BSA. Plates were incubated for 90 min at RT before being washed three times with PBS/0.1T. Each well then received 50 L of 1.3 g/mL polyclonal rabbit anti-mouse IgG conjugated to HRP (Dako) in PBS+1% BSA. The plates were then incubated for 1 h at RT. After three washes with PBS/0.1T, ABTS (50 L/well) was added as substrate (Sigma-Aldrich) and color was allowed to develop for 30 min Absorbance was measured at 405 nm. All sera were tested in duplicate. Negative controls included PBS instead of sera as well as plates not coated with the peptide. Sera from mice shown to be culture positive for B. afzelii infection were used as positive controls.

[0313] qPCR Targeting recA

[0314] Oligonucleotide primers were designed for the recA gene in a manner that they could be used in qPCR for identification of all relevant Borrelia species causing Lyme borreliosis (forward: CATGCTCTTGATCCTGTTTA, SEQ ID NO: 213 reverse: CCCATTTCTCCATCTATCTC, SEQ ID NO: 215). The recA fragment was cloned from the B. burgdorferi s.s. strain N40 into pET28b(+), to be used as standard in each reaction. The chromosomal DNA extracted from mouse ears was diluted 1:8 in water in order to reduce matrix effects observed with undiluted DNA. A master mix consisting of 10 L, SSoAdvanced SYBR Green Supermix, 0.3 L, of each primer (10 M), and 7.4 L, water was prepared for each experiment. Eighteen L, of master mix was mixed with 2 L, of the diluted DNA extracted from either bladder or ear in micro-titer plates and the DNA was amplified using a CFX96 real-time PCR detection system (Bio-Rad, USA). The DNA was denatured for 3 minutes at 95 C., followed by 50 cycles of 15 seconds at 95 C. and 30 seconds at 55 C. After amplification, the DNA was prepared for the melting curve analysis by denaturation for 30 seconds at 95 C. followed by 2 minutes at 55 C. The melting curve analysis was performed by 5 seconds incubation at 55 C., with a 0.5 C. increase per cycle, and 5 seconds at 95 C. On each plate, four no-template controls (NTC) were included as well as a standard curve in duplicate with template copy numbers ranging from 10 to 10,000.

[0315] Results

[0316] The lipidated His-tagged mutant OspA fragment heterodimer (Lip-S1D1-S2D1-His) was tested for protective capacity in six separate experiments. Mice were challenged with either the B. burgdorferi s.s. strain N40 (needle challenge) or the B. afzelii strain IS1 (tick challenge) in three experiments each. All experiments included mice immunized with the individual respective lipidated His-tagged mutant OspA monomers as positive control groups (Lip-S1D1-His and Lip-S2D1-His) and mice immunized with adjuvant alone as a negative control group. For challenge with ticks, 1-2 ticks were applied per mouse and only mice from which at least one tick fed until fully engorged were included in the final readout. However, no distinction was made between mice from which one or two fully fed ticks were collected. The protection data from the six experiments are summarized in Table 4.

[0317] The lipidated His-tagged OspA heterodimer (Lip-S1D1-S2D1-His) showed highly statistically-significant protection (Fisher's exact test, two-tailed) in all six experiments against both challenge species as compared to the negative control group. The infectious status of each mouse was determined using either VlsE ELISA alone (experiments 1-3) or in combination with recA qPCR (experiments 4-6). In cases where both methods were used, a mouse was regarded as infected when at least one method gave a positive result. The level of protection conferred by the lipidated His-tagged mutant OspA fragment heterodimer (Lip-S1D1-S2D1-His) was equal to or better than the protection conferred by either of the lipidated His-tagged mutant OspA fragment monomers individually.

Example 5. Protection of Mice from Infection with Borrelia by Immunization with Lipidated Non-his-Tagged Mutant OspA Fragment Heterodimers of Different Serotypes

[0318] Cloning and Expression of Lipidated Non-his-Tagged Mutant OspA Fragment Heterodimers

[0319] The constructs made as described in Example 4 were used for the generation of His-less constructs by the introduction of a stop codon by PCR amplification. Gene fragments were cloned into the pET28b(+) vector (Novagen), a vector containing a Kanamycin resistance cassette as well as a T7 promoter. The lipoproteins of the stabilized heterodimers were expressed in BL21 Star(DE3) cells (Invitrogen) and after induction by IPTG, the growth temperature of the cells was lowered from 37 C. to 25 C. to promote efficient post-translational processing of the proteins. Cells were collected after 4 h by centrifugation and the pellet was stored at 70 C. for up to 12 months prior to further processing.

[0320] Purification of Lipidated Non-his-Tagged Mutant OspA Fragment Heterodimers

[0321] Cells were disrupted mechanically by high-pressure homogenization and the lipidated mutant OspA fragment heterodimers were enriched in the lipid phase by phase separation, using Triton X-114 as detergent. Subsequently, the diluted detergent phase was subjected to anion exchange chromatography. The resulting flow-through was subjected to cation exchange chromatography and the lipidated proteins eluted from the column. The eluate was subjected to further purification over a gel filtration column (Superdex 200, GE Healthcare) followed by a buffer exchange column (Sephadex G-25, GE Healthcare). The lipidated mutant OspA heterodimer peaks were pooled on the basis of the analytical size exclusion column and reversed phase chromatography. After sterile filtration, the purified heterodimers were stored at 20 C. until formulation.

[0322] Immunization of Mice

[0323] Female C3H/HeN mice will be used for all studies. Prior to each challenge, groups of ten 8-week-old mice will be bled via the facial vein and pre-immune sera will be prepared and pooled. Three s.c. immunizations of 100 L each will be administered at two week intervals. Each dose will contain 5 g of the respective heterodimer proteins: Lip-S1D1-S2D1 (SEQ ID NO: 186), Lip-S4D1-S3D1 (SEQ ID NO: 194) and Lip-S5D1-S6D1 (SEQ ID NO: 190) or 2.5 g of the respective monomer proteins, formulated with aluminium hydroxide (Al(OH).sub.3) at a final concentration of 0.15%. One week after the third immunization, blood will be collected from the facial vein and hyper-immune sera will be prepared. In each experiment, one group immunized with PBS formulated with Al(OH).sub.3 will be included as a negative control. All animal experiments will be conducted in accordance with Austrian law (BGB1 Nr. 501/1989) and approved by Magistratsabteilung 58.

[0324] Needle Challenge of Immunized Mice with In Vitro Grown Borrelia

[0325] Two weeks after the last immunization, the mice will be challenged s.c. with Borrelia diluted in 100 L Borrelia growth medium (BSKII). The challenge doses are strain-dependent, the virulence of the individual strains will require assessment by challenge experiments for determination of ID.sub.50. Doses employed for needle challenge experiments will range from 20 to 50 times the ID.sub.50. Four weeks after needle challenge, mice will be sacrificed and blood and tissues will be collected for readout methods to determine the infection status.

SEQUENCES

[0326]

TABLE-US-00011 SEQIDNO:1 S2D0-His aminoacidsofpositions131-273ofBorrelia afzeliistrainK78,OspAserotype2,wild-type sequence,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:2 S2D1-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype1(aa182 and269),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALKG LEHHHHHH SEQIDNO:3 S2D2-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype2(aa182 and272),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNACKG LEHHHHHH SEQIDNO:4 S2D3-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype3(aa244 and259),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTICVQKYDSAGTNLEGTCVEIKTLDELKNALKG LEHHHHHH SEQIDNO:5 S2D4-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype4(aa141 and241),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:6 S2D5-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype5(aa165 and265),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNCTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTCDELKNALKG LEHHHHHH SEQIDNO:7 S2D6-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype6(aa 185and272),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTCTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNACKG LEHHHHHH SEQIDNO:8 S2D7-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype7(aa199 and223),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTCALNDTNTTQATKKTGAWDSKTSTCTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:9 S2D8-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype8(aa243 and262),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTCTVQKYDSAGTNLEGTAVECKTLDELKNALKG LEHHHHHH SEQIDNO:10 S2D9-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype9(aa184 and204),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGCVTLSKEIAKSGEVTVALNDCNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:11 S2D10-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype10(aa 201and214),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVACNDTNTTQATKKTCAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:12 S2D11-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype11(aa 246and259),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVCKYDSAGTNLEGTCVEIKTLDELKNALKG LEHHHHHH SEQIDNO:13 S2D12-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype12(aa 167and178),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTCEGKVANDKVTC EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALKG LEHHHHHH SEQIDNO:14 BorreliaOspAlipidationsignal MKKYLLGIGLILALIA SEQIDNO:15 BorreliaOspBlipidationsignal MRLLIGFALALALIG SEQIDNO:16 E.colilpplipidationsignal MKATKLVLGAVILGSTLLAG SEQIDNO:17 hLFA-1-likesequencefromB.burgdorferis.s. strainB31 GYVLEGTLTAE SEQIDNO:18 Non-hLFA-1-likesequencefromB.afzelii strainK78 NFTLEGKVAND SEQIDNO:19 B.afzelii(strainK78;OspAserotype2)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSASVDLPGEMKVLVSKEKDK DGKYSLKATVDKIELKGTSDKDNGSGVLEGTKDDKSKAKLTIADDLSK TTFELFKEDGKTLVSRKVSSKDKTSTDEMFNEKGELSAKTMTRENGTK LEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKEIA KSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQ DTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:20 B.burgdorferis.s.(strainB31,OspAserotype 1)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGEMKVLVSKEKNK DGKYDLIATVDKLELKGTSDKNNGSGVLEGVKADKSKVKLTISDDLGQ TTLEVFKEDGKTLVSKKVTSKDKSSTEEKFNEKGEVSEKIITRADGTR LEYTGIKSDGSGKAKEVLKGYVLEGTLTAEKTTLVVKEGTVTLSKNIS KSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFTKE NTITVQQYDSNGTKLEGSAVEITKLDEIKNALK SEQIDNO:21 B.garinii(strainPBr,OspAserotype3)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGGMKVLVSKEKDK DGKYSLMATVEKLELKGTSDKSNGSGVLEGEKADKSKAKLTISQDLNQ TTFEIFKEDGKTLVSRKVNSKDKSSTEEKFNDKGKLSEKVVTRANGTR LEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSKNI SKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVFTK ENTITVQNYNRAGNALEGSPAEIKDLAELKAALK SEQIDNO:22 B.bavariensis(strainPBi,OspAserotype4) OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGEMKVLVSKEKDK DGKYSLMATVDKLELKGTSDKSNGSGTLEGEKSDKSKAKLTISEDLSK TTFEIFKEDGKTLVSKKVNSKDKSSIEEKFNAKGELSEKTILRANGTR LEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSKHIP NSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVFTKE DTITVQKYDSAGTNLEGNAVEIKTLDELKNALK SEQIDNO:23 B.garinii(strainPHei,OspAserotype5)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGGMKVLVSKEKDK DGKYSLMATVEKLELKGTSDKNNGSGTLEGEKTDKSKVKLTIAEDLSK TTFEIFKEDGKTLVSKKVTLKDKSSTEEKFNEKGEISEKTIVRANGTR LEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLSKNI SKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVFTKE DTITVQNYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:24 B.garinii(strainDK29,OspAserotype6)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGGMTVLVSKEKDK DGKYSLEATVDKLELKGTSDKNNGSGTLEGEKTDKSKVKSTIADDLSQ TKFEIFKEDGKTLVSKKVTLKDKSSTEEKFNGKGETSEKTIVRANGTR LEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSKNI LKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVFTK EDTITVQRYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:25 B.garinii(strainT25,OspAserotype7)OspA MKKYLLGIGLILALIACKQNVSSLDEKNSVSVDLPGEMKVLVSKEKDK DGKYSLEATVDKLELKGTSDKNNGSGVLEGVKAAKSKAKLTIADDLSQ TKFEIFKEDGKTLVSKKVTLKDKSSTEEKFNDKGKLSEKVVTRANGTR LEYTEIQNDGSGKAKEVLKSLTLEGTLTADGETKLTVEAGTVTLSKNI SESGEITVELKDTETTPADKKSGTWDSKTSTLTISKNSQKTKQLVFTK ENTITVQKYNTAGTKLEGSPAEIKDLEALKAALK SEQIDNO:26 Borrelianestedpcrdetectionforwardprimer1 GTATGTTTAGTGAGGGGGGTG SEQIDNO:27 Borrelianestedpcrdetectionreverseprimer1 GGATCATAGCTCAGGTGGTTAG SEQIDNO:28 Borrelianestedpcrdetectionforwardprimer2 AGGGGGGTGAAGTCGTAACAAG SEQIDNO:29 Borrelianestedpcrdetectionreverseprimer2 GTCTGATAAACCTGAGGTCGGA SEQIDNO:30 25-merpeptide MKKDDQIAAAMVLRGMAKDGQFALK SEQIDNO:31 Mousecathelin RLAGLLRKGGEKIGEKLKKIGQKIKNFFQKLVPQPE SEQIDNO:32 5-(dIdC).sub.13-3 dIdCdIdCdIdCdIdCdIdCdIdCdIdCdIdCdIdC dIdCdIdCdIdCdIdC SEQIDNO:33 KLKpeptide KLKLLLLLKLK SEQIDNO:34 B.afzelii(strainK78,serotype2),OspAaa 126-273 FNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVAN DKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTS TLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELK NALK SEQIDNO:35 B.afzelii(strainK78,serotype2),OspAaa 131-273 ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:36 peptidelinker GGGGGGGG SEQIDNO:37 peptidelinker2 GGGGGGGGGGGG SEQIDNO:38 peptidelinker3 GAGA SEQIDNO:39 peptidelinker4 GAGAGAGA SEQIDNO:40 peptidelinker5 GAGAGAGAGAGA SEQIDNO:41 peptidelinker6 GGGSGGGS SEQIDNO:42 peptidelinker7 GGGSGGGSGGGS SEQIDNO:43 S1D4-S2D4_aa HeterodimerfusionproteinofOspAserotypes1 and2bothwithdisulfidebondtype4,LN1 peptidelinker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18) FNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTLEGKVAN DKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAAWNSGTS TLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEITKLDEIK NALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECGTKLEYT EMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKEIAKSGE VTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQCTIT VQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:44 Lip-S1D4-S2D4_nt CodingsequenceforfusionproteinsofOspA serotypes1and2bothwithdisulfidebondtype 4,E.colilpplipidationsignal,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCTCGGAA AAAATCATTACCCGTGCTTGCGGCACCCGTCTGGAATACACCGGCATT AAATCGGATGGCAGCGGCAAAGCGAAGGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAGACCACCCTGGTGGTGAAAGAA GGCACCGTTACGCTGAGCAAAAACATTAGTAAGTCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAAAAGACGGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATTCCAAA AAGACCAAAGATCTGGTCTTCACGAAAGAATGCACCATCACGGTGCAG CAATATGACAGCAACGGTACCAAACTGGAAGGCTCTGCGGTGGAAATC ACGAAACTGGATGAAATCAAAAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAATGC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAAGAAGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAACAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAATGTACGATCACCGTGCAGAAATACGATAGTGCGGGTACC AACCTGGAAGGCACCGCTGTTGAAATCAAAACCCTGGACGAACTGAAA AACGCCCTGAAA SEQIDNO:45 Lip-S1D4-S2D4_His_aa HeterodimerfusionproteinofOspAserotypes1 and2bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,N-terminal lipidation,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND(SEQIDNO:18), C-terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEIT KLDEIKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALKGLEHHHHHH SEQIDNO:46 Lip-S1D4-S2D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes1and2bothwithdisulfide bondtype4,E.colilpplipidationsignal,LN1 peptidelinker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCTCGGAA AAAATCATTACCCGTGCTTGCGGCACCCGTCTGGAATACACCGGCATT AAATCGGATGGCAGCGGCAAAGCGAAGGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAGACCACCCTGGTGGTGAAAGAA GGCACCGTTACGCTGAGCAAAAACATTAGTAAGTCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAAAAGACGGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATTCCAAA AAGACCAAAGATCTGGTCTTCACGAAAGAATGCACCATCACGGTGCAG CAATATGACAGCAACGGTACCAAACTGGAAGGCTCTGCGGTGGAAATC ACGAAACTGGATGAAATCAAAAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAATGC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAAGAAGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAACAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAATGTACGATCACCGTGCAGAAATACGATAGTGCGGGTACC AACCTGGAAGGCACCGCTGTTGAAATCAAAACCCTGGACGAACTGAAA AACGCCCTGAAAGGCCTCGAGCACCACCACCACCACCAC SEQIDNO:47 S1D1-S2D1_aa HeterodimerfusionproteinofOspAserotype1 andOspAserotype2withdisulfidebondtype1, LN1peptidelinker(SEQIDNO:184),aa164-174 ofOspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18) FNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTLEGKVAN DKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAAWNSGTS TLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEITKLDEIC NALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENGTKLEYT EMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKEIAKSGE VTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQDTIT VQKYDSAGTNLEGTAVEIKTLDELCNALK SEQIDNO:48 Lip-S1D1-S2D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype1 andOspAserotype2withdisulfidebondtype1, E.colilpplipidationsignal,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCAGCGAA AAAATCATTACCCGCGCAGACGGCACCCGCCTGGAATACACCGGCATC AAATCGGACGGCAGCGGCAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAAACCACCCTGGTGGTGAAATGC GGCACCGTTACGCTGAGCAAAAACATTAGTAAATCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAGAAAACCGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATAGCAAG AAAACCAAAGATCTGGTCTTCACGAAAGAAAACACCATCACGGTGCAG CAATATGACAGCAATGGTACCAAACTGGAAGGCTCCGCTGTGGAAATC ACGAAACTGGATGAAATCTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAAAAC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAATGCGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAATAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAAGATACGATCACCGTGCAGAAATACGACAGTGCGGGTACC AACCTGGAAGGCACGGCTGTTGAAATCAAAACCCTGGACGAACTGTGT AACGCCCTGAAA SEQIDNO:49 Lip-S1D1-S2D1_His_aa HeterodimerfusionproteinofOspAserotype1 andOspAserotype2withdisulfidebondtype1, N-terminalCSSforadditionoflipids,N- terminallipidation,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEIT KLDEICNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALKGLEHHHHHH SEQIDNO:50 Lip-S1D1-S2D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype1andOspAserotype2 withdisulfidebondtype1,E.colilpp lipidationsignal,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCAGCGAA AAAATCATTACCCGCGCAGACGGCACCCGCCTGGAATACACCGGCATC AAATCGGACGGCAGCGGCAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAAACCACCCTGGTGGTGAAATGC GGCACCGTTACGCTGAGCAAAAACATTAGTAAATCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAGAAAACCGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATAGCAAG AAAACCAAAGATCTGGTCTTCACGAAAGAAAACACCATCACGGTGCAG CAATATGACAGCAATGGTACCAAACTGGAAGGCTCCGCTGTGGAAATC ACGAAACTGGATGAAATCTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAAAAC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAATGCGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAATAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAAGATACGATCACCGTGCAGAAATACGACAGTGCGGGTACC AACCTGGAAGGCACGGCTGTTGAAATCAAAACCCTGGACGAACTGTGT AACGCCCTGAAAGGCCTCGAGCACCACCACCACCACCAC SEQIDNO:51 S3D4-S4D4_aa HeterodimerfusionproteinofOspAserotype3 andOspAserotype4withdisulfidebondtype 4,LN1peptidelinker(SEQIDNO:184) FNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFALEGTLTD GGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTGEWKSDT STLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEIKDLAEL KAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRACGTRLEY TEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSKHIPNSG EITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVFTKECTI TVQKYDSAGTNLEGNAVEIKTLDELKNALK SEQIDNO:52 Lip-S3D4-S4D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype3 andOspAserotype4withdisulfidebondtype4, E.colilpplipidationsignal,LN1peptide linker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCAGAA AAAGTGGTCACCCGCGCTTGTGGCACCCGCCTGGAATACACCGAAATC AAAAACGACGGCTCGGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG GAAGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAATGCACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCCCCGGCTGAA ATCAAGGACCTGGCGGAACTGAAGGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGTCGGAAAAAACCATCCTGCGCGCC TGTGGCACCCGCCTGGAATACACGGAAATCAAGTCGGACGGCACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCGACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAATGCACGATCACCGTTCAAAAATATGATTCCGCAGGT ACCAACCTGGAAGGCAACGCTGTGGAAATCAAAACCCTGGACGAACTG AAAAATGCTCTGAAG SEQIDNO:53 Lip-S3D4-S4D4_His_aa HeterodimerfusionproteinofOspAserotype3 andOspAserotype4withdisulfidebondtype 4,N-terminalCSSforadditionoflipids,N- terminallipidation,LN1peptidelinker (SEQIDNO:184),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEI KDLAELKAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAC GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKECTITVQKYDSAGTNLEGNAVEIKTLDELKNALKGLEHHHHHH SEQIDNO:54 Lip-S3D4-S4D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype3andOspAserotype4with disulfidebondtype4,E.colilpplipidation signal,N-terminalCSSforadditionoflipids, LN1peptidelinker(SEQIDNO:184),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCAGAA AAAGTGGTCACCCGCGCTTGTGGCACCCGCCTGGAATACACCGAAATC AAAAACGACGGCTCGGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG GAAGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAATGCACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCCCCGGCTGAA ATCAAGGACCTGGCGGAACTGAAGGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGTCGGAAAAAACCATCCTGCGCGCC TGTGGCACCCGCCTGGAATACACGGAAATCAAGTCGGACGGCACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCGACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAATGCACGATCACCGTTCAAAAATATGATTCCGCAGGT ACCAACCTGGAAGGCAACGCTGTGGAAATCAAAACCCTGGACGAACTG AAAAATGCTCTGAAGGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:55 S3D1-S4D1_aa HeterodimerfusionproteinofOspAserotypes3 and4bothwithdisulfidebondtype1,LN1 peptidelinker(SEQIDNO:184) FNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFALEGTLTD GGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTGEWKSDT STLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEIKDLAEL CAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRANGTRLEY TEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSKHIPNSG EITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVFTKEDTI TVQKYDSAGTNLEGNAVEIKTLDELCNALK SEQIDNO:56 Lip-S3D1-S4D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes3 and4bothwithdisulfidebondtype1,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCGGAA AAAGTGGTCACCCGCGCAAATGGCACCCGCCTGGAATACACGGAAATC AAAAACGATGGTAGCGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG TGCGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAAAACACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCACCGGCTGAA ATCAAGGACCTGGCTGAACTGTGTGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGAGCGAAAAAACGATCCTGCGTGCG AATGGCACCCGTCTGGAATACACCGAAATCAAATCCGATGGTACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCAACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAAGATACGATCACCGTTCAAAAATATGACTCCGCGGGC ACCAACCTGGAAGGCAATGCCGTCGAAATCAAAACCCTGGATGAACTG TGTAATGCTCTGAAG SEQIDNO:57 Lip-S3D1-S4D1_His_aa HeterodimerfusionproteinofOspAserotypes3 and4bothwithdisulfidebondtype1,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,N-terminallipidation,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEI KDLAELCAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAN GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKEDTITVQKYDSAGTNLEGNAVEIKTLDELCNALKGLEHHHHHH SEQIDNO:58 Lip-S3D1-S4D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes3and4bothwithdisulfide bondtype1,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCGGAA AAAGTGGTCACCCGCGCAAATGGCACCCGCCTGGAATACACGGAAATC AAAAACGATGGTAGCGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG TGCGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAAAACACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCACCGGCTGAA ATCAAGGACCTGGCTGAACTGTGTGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGAGCGAAAAAACGATCCTGCGTGCG AATGGCACCCGTCTGGAATACACCGAAATCAAATCCGATGGTACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCAACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAAGATACGATCACCGTTCAAAAATATGACTCCGCGGGC ACCAACCTGGAAGGCAATGCCGTCGAAATCAAAACCCTGGATGAACTG TGTAATGCTCTGAAGGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:59 S5D4-S6D4_aa HeterodimerfusionproteinOspAserotypes5and 6bothwithdisulfidebondtype4,LN1peptide linker(SEQIDNO:184) FNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGTWDSGTS TLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEITTLKELK NALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACGTRLEYT DIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSKNILKSG EITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVFTKECTI TVQRYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:60 Lip-S5D4-S6D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsOspAserotypes5 and6bothwithdisulfidebondtype4,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCAGTGAA AAAACCATTGTGCGTGCGTGTGGCACCCGTCTGGAATATACCGACATC AAGAGCGATAAAACGGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC GAAGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGACTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAATGCACGATCACCGTGCAA AACTATGATAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGTGAAAAAACGATTGTTCGCGCCTGT GGCACCCGCCTGGAATACACGGATATCAAGTCGGATGGTTCGGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGACAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAATGCACGATCACCGTTCAACGCTATGATAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAA SEQIDNO:61 Lip-S5D4-S6D4_His_aa HeterodimerfusionproteinOspAserotypes5and 6bothwithdisulfidebondtype4,N-terminal CSSforadditionoflipids,N-terminal lipidation,LN1peptidelinker(SEQIDNO:184), C-terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEIT TLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKECTITVQRYDSAGTNLEGKAVEITTLKELKNALKGLEHHHHHH SEQIDNO:62 Lip-S5D4-S6D4_His_nt Codingsequenceforheterodimerfusionprotein OspAserotypes5and6bothwithdisulfide bondtype4,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCAGTGAA AAAACCATTGTGCGTGCGTGTGGCACCCGTCTGGAATATACCGACATC AAGAGCGATAAAACGGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC GAAGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGACTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAATGCACGATCACCGTGCAA AACTATGATAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGTGAAAAAACGATTGTTCGCGCCTGT GGCACCCGCCTGGAATACACGGATATCAAGTCGGATGGTTCGGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGACAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAATGCACGATCACCGTTCAACGCTATGATAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:63 S5D1-S6D1_aa HeterodimerfusionproteinofOspAserotypes6 bothwithdisulfidebondtype1,LN1peptide linker(SEQIDNO:184) FNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAA DGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGTWDSGTS TLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEITTLKELC NALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANGTRLEYT DIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSKNILKSG EITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVFTKEDTI TVQRYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:64 Lip-S5D1-S6D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes6 bothwithdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCTCAGAA AAAACCATCGTCCGCGCTAACGGCACCCGCCTGGAATACACCGACATC AAATCAGACAAGACCGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC TGCGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGATTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAAGATACGATCACCGTGCAA AACTATGACAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGCGAAAAGACCATCGTGCGTGCGAAC GGTACCCGCCTGGAATATACGGACATTAAATCGGACGGCAGCGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGATAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAAGATACGATCACCGTTCAACGCTATGACAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAA SEQIDNO:65 Lip-S5D1-S6D1_His_aa HeterodimerfusionproteinofOspAserotypes6 bothwithdisulfidebondtype1,N-terminalCSS foradditionoflipids,N-terminallipidation, LN1peptidelinker(SEQIDNO:184),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEIT TLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKEDTITVQRYDSAGTNLEGKAVEITTLKELCNALKGLEHHHHHH SEQIDNO:66 Lip-S5D1-S6D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes6bothwithdisulfidebond type1,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCTCAGAA AAAACCATCGTCCGCGCTAACGGCACCCGCCTGGAATACACCGACATC AAATCAGACAAGACCGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC TGCGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGATTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAAGATACGATCACCGTGCAA AACTATGACAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGCGAAAAGACCATCGTGCGTGCGAAC GGTACCCGCCTGGAATATACGGACATTAAATCGGACGGCAGCGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGATAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAAGATACGATCACCGTTCAACGCTATGACAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:67 S2D4-S1D4_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype4,LN1 peptidelinker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18) FNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVAN DKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTS TLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDELK NALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACGTRLEYT GIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKNISKSGE VSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFTKECTIT VQQYDSNGTKLEGSAVEITKLDEIKNALK SEQIDNO:68 Lip-S2D4-S1D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes2 and1bothwithdisulfidebondtype4,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAATGCGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAAGAA GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAACAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAATGTACGATCACCGTGCAG AAATACGATAGTGCGGGTACCAACCTGGAAGGCACCGCTGTTGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCTCGGAAAAAATCATTACCCGTGCTTGC GGCACCCGTCTGGAATACACCGGCATTAAATCGGATGGCAGCGGCAAA GCGAAGGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAGACCACCCTGGTGGTGAAAGAAGGCACCGTTACGCTGAGCAAA AACATTAGTAAGTCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAAAAGACGGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATTCCAAAAAGACCAAAGATCTGGTCTTC ACGAAAGAATGCACCATCACGGTGCAGCAATATGACAGCAACGGTACC AAACTGGAAGGCTCTGCGGTGGAAATCACGAAACTGGATGAAATCAAA AATGCACTGAAA SEQIDNO:69 Lip-S2D4-S1D4_His_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,N-terminal lipidation,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KECTITVQQYDSNGTKLEGSAVEITKLDEIKNALKGLEHHHHHH SEQIDNO:70 Lip-S2D4-S1D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes2and1bothwithdisulfide bondtype4,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAATGCGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAAGAA GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAACAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAATGTACGATCACCGTGCAG AAATACGATAGTGCGGGTACCAACCTGGAAGGCACCGCTGTTGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCTCGGAAAAAATCATTACCCGTGCTTGC GGCACCCGTCTGGAATACACCGGCATTAAATCGGATGGCAGCGGCAAA GCGAAGGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAGACCACCCTGGTGGTGAAAGAAGGCACCGTTACGCTGAGCAAA AACATTAGTAAGTCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAAAAGACGGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATTCCAAAAAGACCAAAGATCTGGTCTTC ACGAAAGAATGCACCATCACGGTGCAGCAATATGACAGCAACGGTACC AAACTGGAAGGCTCTGCGGTGGAAATCACGAAACTGGATGAAATCAAA AATGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:71 S2D1-S1D1_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) FNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVAN DKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTS TLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELC NALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADGTRLEYT GIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKNISKSGE VSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFTKENTIT VQQYDSNGTKLEGSAVEITKLDEICNALK SEQIDNO:72 Lip-S2D1-S1D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes2 and1bothwithdisulfidebondtype1,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAAAACGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAATGC GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAATAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAAGATACGATCACCGTGCAG AAATACGACAGTGCGGGTACCAACCTGGAAGGCACGGCTGTTGAAATC AAAACCCTGGACGAACTGTGTAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCAGCGAAAAAATCATTACCCGCGCAGAC GGCACCCGCCTGGAATACACCGGCATCAAATCGGACGGCAGCGGCAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAAACCACCCTGGTGGTGAAATGCGGCACCGTTACGCTGAGCAAA AACATTAGTAAATCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAGAAAACCGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATAGCAAGAAAACCAAAGATCTGGTCTTC ACGAAAGAAAACACCATCACGGTGCAGCAATATGACAGCAATGGTACC AAACTGGAAGGCTCCGCTGTGGAAATCACGAAACTGGATGAAATCTGT AATGCACTGAAA SEQIDNO:73 Lip-S2D1-S1D1_His_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),N-terminal lipidation,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KENTITVQQYDSNGTKLEGSAVEITKLDEICNALKGLEHHHHHH SEQIDNO:74 Lip-S2D1-S1D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes2and1bothwithdisulfide bondtype1,E.colilpplipidationsignal, N-terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAAAACGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAATGC GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAATAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAAGATACGATCACCGTGCAG AAATACGACAGTGCGGGTACCAACCTGGAAGGCACGGCTGTTGAAATC AAAACCCTGGACGAACTGTGTAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCAGCGAAAAAATCATTACCCGCGCAGAC GGCACCCGCCTGGAATACACCGGCATCAAATCGGACGGCAGCGGCAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAAACCACCCTGGTGGTGAAATGCGGCACCGTTACGCTGAGCAAA AACATTAGTAAATCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAGAAAACCGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATAGCAAGAAAACCAAAGATCTGGTCTTC ACGAAAGAAAACACCATCACGGTGCAGCAATATGACAGCAATGGTACC AAACTGGAAGGCTCCGCTGTGGAAATCACGAAACTGGATGAAATCTGT AATGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:75 S4D4-S3D4_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184) FNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFALEGTLAA DKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGKWDSNTS TLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIKTLDELK NALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACGTRLEYT EIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSKNISKSG EITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVFTKECTI TVQNYNRAGNALEGSPAEIKDLAELKAALK SEQIDNO:76 Lip-S4D4-S3D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes4 and3bothwithdisulfidebondtype4,E.coli 1pplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGCTAAAGGTGAACTGTCGGAA AAAACCATCCTGCGCGCCTGTGGCACCCGCCTGGAATACACGGAAATC AAGTCGGACGGCACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGGAA GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCGACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAATGCACGATCACCGTTCAA AAATATGATTCCGCAGGTACCAACCTGGAAGGCAACGCTGTGGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCAGAAAAAGTGGTCACCCGCGCTTGT GGCACCCGCCTGGAATACACCGAAATCAAAAACGACGGCTCGGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGGAAGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAATGCACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCCCCGGCTGAAATCAAGGACCTGGCGGAACTG AAGGCGGCACTGAAA SEQIDNO:77 Lip-S4D4-S3D4_His_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminal lipidation,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKECTITVQNYNRAGNALEGSPAEIKDLAELKAALKGLEHHHHHH SEQIDNO:78 Lip-S4D4-S3D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes4and3bothwithdisulfide bondtype4,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGCTAAAGGTGAACTGTCGGAA AAAACCATCCTGCGCGCCTGTGGCACCCGCCTGGAATACACGGAAATC AAGTCGGACGGCACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGGAA GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCGACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAATGCACGATCACCGTTCAA AAATATGATTCCGCAGGTACCAACCTGGAAGGCAACGCTGTGGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCAGAAAAAGTGGTCACCCGCGCTTGT GGCACCCGCCTGGAATACACCGAAATCAAAAACGACGGCTCGGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGGAAGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAATGCACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCCCCGGCTGAAATCAAGGACCTGGCGGAACTG AAGGCGGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:79 S4D1-S3D1_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype1,LN1 peptidelinker(SEQIDNO:184) FNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFALEGTLAA DKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGKWDSNTS TLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIKTLDELC NALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANGTRLEYT EIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSKNISKSG EITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVFTKENTI TVQNYNRAGNALEGSPAEIKDLAELCAALK SEQIDNO:80 Lip-S4D1-S3D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes4 and3bothwithdisulfidebondtype1,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAATGCTAAGGGCGAACTGAGCGAA AAAACGATCCTGCGTGCGAATGGCACCCGTCTGGAATACACCGAAATC AAATCCGATGGTACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGTGC GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCAACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAAGATACGATCACCGTTCAA AAATATGACTCCGCGGGCACCAACCTGGAAGGCAATGCCGTCGAAATC AAAACCCTGGATGAACTGTGTAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCGGAAAAAGTGGTCACCCGCGCAAAT GGCACCCGCCTGGAATACACGGAAATCAAAAACGATGGTAGCGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGTGCGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAAAACACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCACCGGCTGAAATCAAGGACCTGGCTGAACTG TGTGCGGCACTGAAA SEQIDNO:81 Lip-S4D1-S3D1_His_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminal lipidation,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKENTITVQNYNRAGNALEGSPAEIKDLAELCAALKGLEHHHHHH SEQIDNO:82 Lip-S4D1-S3D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes4and3bothwithdisulfide bondtype1,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAATGCTAAGGGCGAACTGAGCGAA AAAACGATCCTGCGTGCGAATGGCACCCGTCTGGAATACACCGAAATC AAATCCGATGGTACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGTGC GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCAACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAAGATACGATCACCGTTCAA AAATATGACTCCGCGGGCACCAACCTGGAAGGCAATGCCGTCGAAATC AAAACCCTGGATGAACTGTGTAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCGGAAAAAGTGGTCACCCGCGCAAAT GGCACCCGCCTGGAATACACGGAAATCAAAAACGATGGTAGCGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGTGCGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAAAACACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCACCGGCTGAAATCAAGGACCTGGCTGAACTG TGTGCGGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:83 S6D4-S5D4_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype4,LN1 peptidelinker(SEQIDNO:184) FNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTGKWDSKT STLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEITTLKEL KNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRACGTRLEY TDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLSKNISKS GEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVFTKECTI TVQNYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:84 Lip-S6D4-S5D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes6 and5bothwithdisulfidebondtype4,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGTGAA AAAACGATTGTTCGCGCCTGTGGCACCCGCCTGGAATACACGGATATC AAGTCGGATGGTTCGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG GAAGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGACAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAATGCACGATCACCGTT CAACGCTATGATAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCAGTGAAAAAACCATTGTGCGTGCG TGTGGCACCCGTCTGGAATATACCGACATCAAGAGCGATAAAACGGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCGAAGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGACTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAATGCACGATCACCGTGCAAAACTATGATAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAA SEQIDNO:85 Lip-S6D4-S5D4_His_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminal lipidation,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEI TTLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAC GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKECTITVQNYDSAGTNLEGKAVEITTLKELKNALKGLEHHHHHH SEQIDNO:86 Lip-S6D4-S5D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes6and5bothwithdisulfide bondtype4,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGTGAA AAAACGATTGTTCGCGCCTGTGGCACCCGCCTGGAATACACGGATATC AAGTCGGATGGTTCGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG GAAGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGACAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAATGCACGATCACCGTT CAACGCTATGATAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCAGTGAAAAAACCATTGTGCGTGCG TGTGGCACCCGTCTGGAATATACCGACATCAAGAGCGATAAAACGGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCGAAGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGACTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAATGCACGATCACCGTGCAAAACTATGATAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:87 S6D1-S5D1_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype1,LN1 peptidelinker(SEQIDNO:184) FNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTLEGTLAA DGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTGKWDSKT STLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEITTLKEL CNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRANGTRLEY TDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLSKNISKS GEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVFTKEDTI TVQNYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:88 Lip-S6D1-S5D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotypes6 and5bothwithdisulfidebondtype1,E.coli lpplipidationsignal,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGCGAA AAGACCATCGTGCGTGCGAACGGTACCCGCCTGGAATATACGGACATT AAATCGGACGGCAGCGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG TGCGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGATAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAAGATACGATCACCGTT CAACGCTATGACAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCTCAGAAAAAACCATCGTCCGCGCT AACGGCACCCGCCTGGAATACACCGACATCAAATCAGACAAGACCGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCTGCGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGATTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAAGATACGATCACCGTGCAAAACTATGACAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAA SEQIDNO:89 Lip-S6D1-S5D1_His_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype1,LN1 peptidelinker(SEQIDNO:184),N-terminal lipidation,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCSSFNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEI TTLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAN GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKEDTITVQNYDSAGTNLEGKAVEITTLKELCNALKGLEHHHHHH SEQIDNO:90 Lip-S6D1-S5D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotypes6and5bothwithdisulfide bondtype1,E.colilpplipidationsignal,N- terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGCGAA AAGACCATCGTGCGTGCGAACGGTACCCGCCTGGAATATACGGACATT AAATCGGACGGCAGCGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG TGCGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGATAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAAGATACGATCACCGTT CAACGCTATGACAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCTCAGAAAAAACCATCGTCCGCGCT AACGGCACCCGCCTGGAATACACCGACATCAAATCAGACAAGACCGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCTGCGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGATTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAAGATACGATCACCGTGCAAAACTATGACAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:91 S1D4-S2D1_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype4andOspAserotype 2withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) FNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTLEGKVAN DKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAAWNSGTS TLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEITKLDEIK NALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENGTKLEYT EMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKEIAKSGE VTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQDTIT VQKYDSAGTNLEGTAVEIKTLDELCNALK SEQIDNO:92 Lip-S1D4-S2D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype1 withdisulfidebondtype4andOspAserotype2 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCTCGGAA AAAATCATTACCCGTGCTTGCGGCACCCGTCTGGAATACACCGGCATT AAATCGGATGGCAGCGGCAAAGCGAAGGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAGACCACCCTGGTGGTGAAAGAA GGCACCGTTACGCTGAGCAAAAACATTAGTAAGTCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAAAAGACGGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATTCCAAA AAGACCAAAGATCTGGTCTTCACGAAAGAATGCACCATCACGGTGCAG CAATATGACAGCAACGGTACCAAACTGGAAGGCTCTGCGGTGGAAATC ACGAAACTGGATGAAATCAAAAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAAAAC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAATGCGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAATAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAAGATACGATCACCGTGCAGAAATACGACAGTGCGGGTACC AACCTGGAAGGCACGGCTGTTGAAATCAAAACCCTGGACGAACTGTGT AACGCCCTGAAA SEQIDNO:93 Lip-S1D4-S2D1_His_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype4andOspAserotype 2withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEIT KLDEIKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALKGLEHHHHHH SEQIDNO:94 Lip-S1D4-S2D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype1withdisulfidebondtype 4andOspAserotype2withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCTCGGAA AAAATCATTACCCGTGCTTGCGGCACCCGTCTGGAATACACCGGCATT AAATCGGATGGCAGCGGCAAAGCGAAGGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAGACCACCCTGGTGGTGAAAGAA GGCACCGTTACGCTGAGCAAAAACATTAGTAAGTCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAAAAGACGGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATTCCAAA AAGACCAAAGATCTGGTCTTCACGAAAGAATGCACCATCACGGTGCAG CAATATGACAGCAACGGTACCAAACTGGAAGGCTCTGCGGTGGAAATC ACGAAACTGGATGAAATCAAAAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAAAAC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAATGCGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAATAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAAGATACGATCACCGTGCAGAAATACGACAGTGCGGGTACC AACCTGGAAGGCACGGCTGTTGAAATCAAAACCCTGGACGAACTGTGT AACGCCCTGAAAGGCCTCGAGCACCACCACCACCACCAC SEQIDNO:95 S1D1-S2D4_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype1andOspAserotype 2withdisulfidebondtype4,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) FNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTLEGKVAN DKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAAWNSGTS TLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEITKLDEIC NALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECGTKLEYT EMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKEIAKSGE VTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQCTIT VQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:96 Lip-S1D1-S2D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype1 withdisulfidebondtype1andOspAserotype2 withdisulfidebondtype4,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCAGCGAA AAAATCATTACCCGCGCAGACGGCACCCGCCTGGAATACACCGGCATC AAATCGGACGGCAGCGGCAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAAACCACCCTGGTGGTGAAATGC GGCACCGTTACGCTGAGCAAAAACATTAGTAAATCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAGAAAACCGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATAGCAAG AAAACCAAAGATCTGGTCTTCACGAAAGAAAACACCATCACGGTGCAG CAATATGACAGCAATGGTACCAAACTGGAAGGCTCCGCTGTGGAAATC ACGAAACTGGATGAAATCTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAATGC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAAGAAGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAACAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAATGTACGATCACCGTGCAGAAATACGATAGTGCGGGTACC AACCTGGAAGGCACCGCTGTTGAAATCAAAACCCTGGACGAACTGAAA AACGCCCTGAAA SEQIDNO:97 Lip-S1D1-S2D4_His_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype1andOspAserotype 2withdisulfidebondtype4,N-terminalCSSfor additionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEIT KLDEICNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALKGLEHHHHHH SEQIDNO:98 Lip-S1D1-S2D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype1withdisulfidebondtype 1andOspAserotype2withdisulfidebondtype 4,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAGTCAGCGAA AAAATCATTACCCGCGCAGACGGCACCCGCCTGGAATACACCGGCATC AAATCGGACGGCAGCGGCAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCAAATGATAAAACCACCCTGGTGGTGAAATGC GGCACCGTTACGCTGAGCAAAAACATTAGTAAATCCGGTGAAGTCTCT GTGGAACTGAATGATACCGACAGCTCTGCGGCCACCAAGAAAACCGCA GCTTGGAACTCAGGCACCTCGACGCTGACCATTACGGTTAATAGCAAG AAAACCAAAGATCTGGTCTTCACGAAAGAAAACACCATCACGGTGCAG CAATATGACAGCAATGGTACCAAACTGGAAGGCTCCGCTGTGGAAATC ACGAAACTGGATGAAATCTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAACTGTCGGCGAAAACGATGACGCGTGAATGC GGCACCAAACTGGAATATACGGAAATGAAAAGCGATGGCACCGGTAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCCAAT GACAAAGTCACCCTGGAAGTGAAAGAAGGCACCGTTACGCTGTCAAAA GAAATTGCAAAATCGGGTGAAGTGACCGTTGCTCTGAACGATACGAAT ACCACGCAAGCGACCAAGAAAACCGGCGCCTGGGACAGCAAAACCTCT ACGCTGACCATTAGTGTTAACAGCAAGAAAACCACGCAGCTGGTCTTC ACCAAACAATGTACGATCACCGTGCAGAAATACGATAGTGCGGGTACC AACCTGGAAGGCACCGCTGTTGAAATCAAAACCCTGGACGAACTGAAA AACGCCCTGAAAGGCCTCGAGCACCACCACCACCACCAC SEQIDNO:99 S3D4-S4D1_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype4andOspAserotype 4withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184) FNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFALEGTLTD GGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTGEWKSDT STLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEIKDLAEL KAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRANGTRLEY TEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSKHIPNSG EITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVFTKEDTI TVQKYDSAGTNLEGNAVEIKTLDELCNALK SEQIDNO:100 Lip-S3D4-S4D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype3 withdisulfidebondtype4andOspAserotype4 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCAGAA AAAGTGGTCACCCGCGCTTGTGGCACCCGCCTGGAATACACCGAAATC AAAAACGACGGCTCGGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG GAAGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAATGCACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCCCCGGCTGAA ATCAAGGACCTGGCGGAACTGAAGGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGAGCGAAAAAACGATCCTGCGTGCG AATGGCACCCGTCTGGAATACACCGAAATCAAATCCGATGGTACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCAACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAAGATACGATCACCGTTCAAAAATATGACTCCGCGGGC ACCAACCTGGAAGGCAATGCCGTCGAAATCAAAACCCTGGATGAACTG TGTAATGCTCTGAAG SEQIDNO:101 Lip-S3D4-S4D1_His_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype4andOspAserotype 4withdisulfidebondtype1,N-terminalCSSfor additionoflipids,LN1peptidelinker(SEQ IDNO:184),N-terminallipidation,C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEI KDLAELKAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAN GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKEDTITVQKYDSAGTNLEGNAVEIKTLDELCNALKGLEHHHHHH SEQIDNO:102 Lip-S3D4-S4D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype3withdisulfidebondtype 4andOspAserotype4withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCAGAA AAAGTGGTCACCCGCGCTTGTGGCACCCGCCTGGAATACACCGAAATC AAAAACGACGGCTCGGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG GAAGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAATGCACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCCCCGGCTGAA ATCAAGGACCTGGCGGAACTGAAGGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGAGCGAAAAAACGATCCTGCGTGCG AATGGCACCCGTCTGGAATACACCGAAATCAAATCCGATGGTACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCAACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAAGATACGATCACCGTTCAAAAATATGACTCCGCGGGC ACCAACCTGGAAGGCAATGCCGTCGAAATCAAAACCCTGGATGAACTG TGTAATGCTCTGAAGGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:103 S3D1-S4D4_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype1andOspAserotype 4withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184) FNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFALEGTLTD GGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTGEWKSDT STLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEIKDLAEL CAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRACGTRLEY TEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSKHIPNSG EITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVFTKECTI TVQKYDSAGTNLEGNAVEIKTLDELKNALK SEQIDNO:104 Lip-S3D1-S4D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype3 withdisulfidebondtype1andOspAserotype4 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCGGAA AAAGTGGTCACCCGCGCAAATGGCACCCGCCTGGAATACACGGAAATC AAAAACGATGGTAGCGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG TGCGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAAAACACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCACCGGCTGAA ATCAAGGACCTGGCTGAACTGTGTGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGTCGGAAAAAACCATCCTGCGCGCC TGTGGCACCCGCCTGGAATACACGGAAATCAAGTCGGACGGCACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCGACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAATGCACGATCACCGTTCAAAAATATGATTCCGCAGGT ACCAACCTGGAAGGCAACGCTGTGGAAATCAAAACCCTGGACGAACTG AAAAATGCTCTGAAG SEQIDNO:105 Lip-S3D1-S4D4_His_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype1andOspAserotype 4withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEI KDLAELCAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAC GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKECTITVQKYDSAGTNLEGNAVEIKTLDELKNALKGLEHHHHHH SEQIDNO:106 Lip-S3D1-S4D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype3withdisulfidebondtype 1andOspAserotype4withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCAAACTGTCGGAA AAAGTGGTCACCCGCGCAAATGGCACCCGCCTGGAATACACGGAAATC AAAAACGATGGTAGCGGCAAAGCGAAGGAAGTTCTGAAAGGCTTTGCC CTGGAAGGTACCCTGACGGATGGCGGTGAAACCAAACTGACCGTGACG TGCGGCACCGTTACGCTGTCTAAAAACATTAGCAAGTCTGGTGAAATC ACGGTCGCACTGAATGATACCGAAACCACGCCGGCTGACAAAAAGACC GGCGAATGGAAAAGTGACACCTCCACGCTGACCATTTCAAAGAACTCG CAGAAACCGAAGCAACTGGTCTTCACCAAAGAAAACACGATCACCGTG CAGAACTATAATCGTGCCGGTAATGCTCTGGAAGGCTCACCGGCTGAA ATCAAGGACCTGGCTGAACTGTGTGCGGCACTGAAAGGCACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGCTAAAGGTGAACTGTCGGAAAAAACCATCCTGCGCGCC TGTGGCACCCGCCTGGAATACACGGAAATCAAGTCGGACGGCACGGGC AAAGCAAAGGAAGTCCTGAAAGATTTTGCTCTGGAAGGTACCCTGGCG GCCGACAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGAGC AAACATATTCCGAACTCTGGTGAAATCACCGTTGAACTGAACGATAGC AATTCTACGCAGGCGACCAAAAAGACGGGCAAATGGGACAGTAATACC TCCACGCTGACCATTTCAGTCAACTCGAAAAAGACCAAAAATATTGTG TTCACGAAGGAATGCACGATCACCGTTCAAAAATATGATTCCGCAGGT ACCAACCTGGAAGGCAACGCTGTGGAAATCAAAACCCTGGACGAACTG AAAAATGCTCTGAAGGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:107 S5D4-S6D1_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype4andOspAserotype 6withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184) FNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGTWDSGTS TLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEITTLKELK NALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANGTRLEYT DIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSKNILKSG EITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVFTKEDTI TVQRYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:108 Lip-S5D4-S6D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype5 withdisulfidebondtype4andOspAserotype6 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCAGTGAA AAAACCATTGTGCGTGCGTGTGGCACCCGTCTGGAATATACCGACATC AAGAGCGATAAAACGGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC GAAGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGACTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAATGCACGATCACCGTGCAA AACTATGATAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGCGAAAAGACCATCGTGCGTGCGAAC GGTACCCGCCTGGAATATACGGACATTAAATCGGACGGCAGCGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGATAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAAGATACGATCACCGTTCAACGCTATGACAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAA SEQIDNO:109 Lip-S5D4-S6D1_His_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype4andOspAserotype 6withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEIT TLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKEDTITVQRYDSAGTNLEGKAVEITTLKELCNALKGLEHHHHHH SEQIDNO:110 Lip-S5D4-S6D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype5withdisulfidebondtype 4andOspAserotype6withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCAGTGAA AAAACCATTGTGCGTGCGTGTGGCACCCGTCTGGAATATACCGACATC AAGAGCGATAAAACGGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC GAAGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGACTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAATGCACGATCACCGTGCAA AACTATGATAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGCGAAAAGACCATCGTGCGTGCGAAC GGTACCCGCCTGGAATATACGGACATTAAATCGGACGGCAGCGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGTGCGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGATAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAAGATACGATCACCGTTCAACGCTATGACAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:111 S5D1-S6D4_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype1andOspAserotype 6withdisulfidebondtype4,LN1peptidelinker (SEQIDNO:184) FNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAA DGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGTWDSGTS TLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEITTLKELC NALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACGTRLEYT DIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSKNILKSG EITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVFTKECTI TVQRYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:112 Lip-S5D1-S6D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype5 withdisulfidebondtype1andOspAserotype6 withdisulfidebondtype4,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCTCAGAA AAAACCATCGTCCGCGCTAACGGCACCCGCCTGGAATACACCGACATC AAATCAGACAAGACCGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC TGCGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGATTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAAGATACGATCACCGTGCAA AACTATGACAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGTGAAAAAACGATTGTTCGCGCCTGT GGCACCCGCCTGGAATACACGGATATCAAGTCGGATGGTTCGGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGACAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAATGCACGATCACCGTTCAACGCTATGATAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAA SEQIDNO:113 Lip-S5D1-S6D4_His_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype1andOspAserotype 6withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEIT TLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKECTITVQRYDSAGTNLEGKAVEITTLKELKNALKGLEHHHHHH SEQIDNO:114 Lip-S5D1-S6D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype5withdisulfidebondtype 1andOspAserotype6withdisulfidebondtype 4,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAGGGCGAAATCTCAGAA AAAACCATCGTCCGCGCTAACGGCACCCGCCTGGAATACACCGACATC AAATCAGACAAGACCGGTAAAGCGAAGGAAGTTCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACC TGCGGTACCGTTACGCTGTCCAAAAACATTAGTAAGTCCGGCGAAATC ACGGTCGCCCTGGATGACACCGATAGCTCTGGCAACAAAAAGAGCGGT ACCTGGGATTCAGGCACCTCGACGCTGACCATTTCTAAAAATCGTACG AAAACCAAGCAGCTGGTCTTCACGAAAGAAGATACGATCACCGTGCAA AACTATGACAGCGCAGGTACCAATCTGGAAGGCAAAGCTGTGGAAATT ACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGGCAAAGGTGAAACGAGTGAAAAAACGATTGTTCGCGCCTGT GGCACCCGCCTGGAATACACGGATATCAAGTCGGATGGTTCGGGCAAA GCAAAGGAAGTCCTGAAAGATTTTACGCTGGAAGGTACCCTGGCAGCA GACGGTAAAACCACGCTGAAGGTGACGGAAGGCACCGTGGTTCTGTCA AAAAACATTCTGAAGTCGGGTGAAATCACCGCAGCTCTGGATGACAGC GATACCACGCGTGCTACGAAAAAGACCGGTAAATGGGACAGCAAGACC TCTACGCTGACCATTAGTGTCAACTCCCAGAAAACGAAGAATCTGGTG TTCACCAAAGAATGCACGATCACCGTTCAACGCTATGATAGTGCGGGC ACCAACCTGGAAGGCAAAGCCGTTGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:115 S2D4-S1D1_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype4andOspAserotype 1withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) FNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVAN DKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTS TLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDELK NALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADGTRLEYT GIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKNISKSGE VSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFTKENTIT VQQYDSNGTKLEGSAVEITKLDEICNALK SEQIDNO:116 Lip-S2D4-S1D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype2 withdisulfidebondtype4andOspAserotype1 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAATGCGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAAGAA GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAACAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAATGTACGATCACCGTGCAG AAATACGATAGTGCGGGTACCAACCTGGAAGGCACCGCTGTTGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCAGCGAAAAAATCATTACCCGCGCAGAC GGCACCCGCCTGGAATACACCGGCATCAAATCGGACGGCAGCGGCAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAAACCACCCTGGTGGTGAAATGCGGCACCGTTACGCTGAGCAAA AACATTAGTAAATCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAGAAAACCGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATAGCAAGAAAACCAAAGATCTGGTCTTC ACGAAAGAAAACACCATCACGGTGCAGCAATATGACAGCAATGGTACC AAACTGGAAGGCTCCGCTGTGGAAATCACGAAACTGGATGAAATCTGT AATGCACTGAAA SEQIDNO:117 Lip-S2D4-S1D1_His_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype4andOspAserotype 1withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),N-terminal lipidation,C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KENTITVQQYDSNGTKLEGSAVEITKLDEICNALKGLEHHHHHH SEQIDNO:118 Lip-S2D4-S1D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype2withdisulfidebondtype 4andOspAserotype1withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAATGCGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAAGAA GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAACAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAATGTACGATCACCGTGCAG AAATACGATAGTGCGGGTACCAACCTGGAAGGCACCGCTGTTGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCAGCGAAAAAATCATTACCCGCGCAGAC GGCACCCGCCTGGAATACACCGGCATCAAATCGGACGGCAGCGGCAAA GCGAAAGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAAACCACCCTGGTGGTGAAATGCGGCACCGTTACGCTGAGCAAA AACATTAGTAAATCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAGAAAACCGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATAGCAAGAAAACCAAAGATCTGGTCTTC ACGAAAGAAAACACCATCACGGTGCAGCAATATGACAGCAATGGTACC AAACTGGAAGGCTCCGCTGTGGAAATCACGAAACTGGATGAAATCTGT AATGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:119 S2D1-S1D4_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype1andOspAserotype 1withdisulfidebondtype4,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18) FNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVAN DKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTS TLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELC NALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACGTRLEYT GIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKNISKSGE VSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFTKECTIT VQQYDSNGTKLEGSAVEITKLDEIKNALK SEQIDNO:120 Lip-S2D1-S1D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype2 withdisulfidebondtype1andOspAserotype1 withdisulfidebondtype4,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184), aa164-174ofOspAserotype1replacedbynon- hLFA-1-likesequenceNFTLEGKVAND(SEQIDNO:18) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAAAACGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAATGC GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAATAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAAGATACGATCACCGTGCAG AAATACGACAGTGCGGGTACCAACCTGGAAGGCACGGCTGTTGAAATC AAAACCCTGGACGAACTGTGTAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCTCGGAAAAAATCATTACCCGTGCTTGC GGCACCCGTCTGGAATACACCGGCATTAAATCGGATGGCAGCGGCAAA GCGAAGGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAGACCACCCTGGTGGTGAAAGAAGGCACCGTTACGCTGAGCAAA AACATTAGTAAGTCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAAAAGACGGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATTCCAAAAAGACCAAAGATCTGGTCTTC ACGAAAGAATGCACCATCACGGTGCAGCAATATGACAGCAACGGTACC AAACTGGAAGGCTCTGCGGTGGAAATCACGAAACTGGATGAAATCAAA AATGCACTGAAA SEQIDNO:121 Lip-S2D1-S1D4_His_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype1andOspAserotype 1withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),N-terminal lipidation,C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) LipCSSFNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KECTITVQQYDSNGTKLEGSAVEITKLDEIKNALKGLEHHHHHH SEQIDNO:122 Lip-S2D1-S1D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype2withdisulfidebondtype 1andOspAserotype1withdisulfidebondtype 4,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18),C-terminal Histag(GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGAAAAAGGCGAACTGTCGGCG AAAACGATGACGCGTGAAAACGGCACCAAACTGGAATATACGGAAATG AAAAGCGATGGCACCGGTAAAGCGAAAGAAGTTCTGAAAAACTTTACC CTGGAAGGCAAAGTCGCCAATGACAAAGTCACCCTGGAAGTGAAATGC GGCACCGTTACGCTGTCAAAAGAAATTGCAAAATCGGGTGAAGTGACC GTTGCTCTGAACGATACGAATACCACGCAAGCGACCAAGAAAACCGGC GCCTGGGACAGCAAAACCTCTACGCTGACCATTAGTGTTAATAGCAAG AAAACCACGCAGCTGGTCTTCACCAAACAAGATACGATCACCGTGCAG AAATACGACAGTGCGGGTACCAACCTGGAAGGCACGGCTGTTGAAATC AAAACCCTGGACGAACTGTGTAACGCCCTGAAAGGCACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTCAACGAAAAAGGCGAAGTCTCGGAAAAAATCATTACCCGTGCTTGC GGCACCCGTCTGGAATACACCGGCATTAAATCGGATGGCAGCGGCAAA GCGAAGGAAGTTCTGAAAAACTTTACCCTGGAAGGCAAAGTCGCAAAT GATAAGACCACCCTGGTGGTGAAAGAAGGCACCGTTACGCTGAGCAAA AACATTAGTAAGTCCGGTGAAGTCTCTGTGGAACTGAATGATACCGAC AGCTCTGCGGCCACCAAAAAGACGGCAGCTTGGAACTCAGGCACCTCG ACGCTGACCATTACGGTTAATTCCAAAAAGACCAAAGATCTGGTCTTC ACGAAAGAATGCACCATCACGGTGCAGCAATATGACAGCAACGGTACC AAACTGGAAGGCTCTGCGGTGGAAATCACGAAACTGGATGAAATCAAA AATGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:123 S4D4-S3D1_aa HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype4andOspAserotype 3withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184) FNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFALEGTLAA DKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGKWDSNTS TLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIKTLDELK NALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANGTRLEYT EIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSKNISKSG EITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVFTKENTI TVQNYNRAGNALEGSPAEIKDLAELCAALK SEQIDNO:124 Lip-S4D4-S3D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype4 withdisulfidebondtype4andOspAserotype3 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGCTAAAGGTGAACTGTCGGAA AAAACCATCCTGCGCGCCTGTGGCACCCGCCTGGAATACACGGAAATC AAGTCGGACGGCACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGGAA GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCGACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAATGCACGATCACCGTTCAA AAATATGATTCCGCAGGTACCAACCTGGAAGGCAACGCTGTGGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCGGAAAAAGTGGTCACCCGCGCAAAT GGCACCCGCCTGGAATACACGGAAATCAAAAACGATGGTAGCGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGTGCGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAAAACACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCACCGGCTGAAATCAAGGACCTGGCTGAACTG TGTGCGGCACTGAAA SEQIDNO:125 Lip-S4D4-S3D1_His_aa HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype4andOspAserotype 3withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminalCSSforadditionof lipids,N-terminallipidation,C-terminalHis tag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKENTITVQNYNRAGNALEGSPAEIKDLAELCAALKGLEHHHHHH SEQIDNO:126 Lip-S4D4-S3D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype4withdisulfidebondtype 4andOspAserotype3withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGCTAAAGGTGAACTGTCGGAA AAAACCATCCTGCGCGCCTGTGGCACCCGCCTGGAATACACGGAAATC AAGTCGGACGGCACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGGAA GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCGACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAATGCACGATCACCGTTCAA AAATATGATTCCGCAGGTACCAACCTGGAAGGCAACGCTGTGGAAATC AAAACCCTGGACGAACTGAAAAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCGGAAAAAGTGGTCACCCGCGCAAAT GGCACCCGCCTGGAATACACGGAAATCAAAAACGATGGTAGCGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGTGCGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAAAACACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCACCGGCTGAAATCAAGGACCTGGCTGAACTG TGTGCGGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:127 S4D1-S3D4_aa HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype1andOspAserotype 3withdisulfidebondtype4,LN1peptidelinker (SEQIDNO:184) FNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFALEGTLAA DKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGKWDSNTS TLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIKTLDELC NALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACGTRLEYT EIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSKNISKSG EITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVFTKECTI TVQNYNRAGNALEGSPAEIKDLAELKAALK SEQIDNO:128 Lip-S4D1-S3D4_nt HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype1andOspAserotype 3withdisulfidebondtype4,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAATGCTAAGGGCGAACTGAGCGAA AAAACGATCCTGCGTGCGAATGGCACCCGTCTGGAATACACCGAAATC AAATCCGATGGTACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGTGC GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCAACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAAGATACGATCACCGTTCAA AAATATGACTCCGCGGGCACCAACCTGGAAGGCAATGCCGTCGAAATC AAAACCCTGGATGAACTGTGTAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCAGAAAAAGTGGTCACCCGCGCTTGT GGCACCCGCCTGGAATACACCGAAATCAAAAACGACGGCTCGGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGGAAGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAATGCACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCCCCGGCTGAAATCAAGGACCTGGCGGAACTG AAGGCGGCACTGAAA SEQIDNO:129 Lip-S4D1-S3D4_His_aa HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype1andOspAserotype 3withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKECTITVQNYNRAGNALEGSPAEIKDLAELKAALKGLEHHHHHH SEQIDNO:130 Lip-S4D1-S3D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype4withdisulfidebondtype 1andOspAserotype3withdisulfidebondtype 4,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAATGCTAAGGGCGAACTGAGCGAA AAAACGATCCTGCGTGCGAATGGCACCCGTCTGGAATACACCGAAATC AAATCCGATGGTACGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTGCT CTGGAAGGTACCCTGGCGGCCGACAAAACCACGCTGAAGGTGACGTGC GGCACCGTGGTTCTGAGCAAACATATTCCGAACTCTGGTGAAATCACC GTTGAACTGAACGATAGCAATTCTACGCAGGCAACCAAAAAGACGGGC AAATGGGACAGTAATACCTCCACGCTGACCATTTCAGTCAACTCGAAA AAGACCAAAAATATTGTGTTCACGAAGGAAGATACGATCACCGTTCAA AAATATGACTCCGCGGGCACCAACCTGGAAGGCAATGCCGTCGAAATC AAAACCCTGGATGAACTGTGTAACGCCCTGAAGGGTACTAGTGACAAA AACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTACTCA TTTAACGATAAGGGCAAACTGTCAGAAAAAGTGGTCACCCGCGCTTGT GGCACCCGCCTGGAATACACCGAAATCAAAAACGACGGCTCGGGCAAA GCGAAGGAAGTTCTGAAAGGCTTTGCCCTGGAAGGTACCCTGACGGAT GGCGGTGAAACCAAACTGACCGTGACGGAAGGCACCGTTACGCTGTCT AAAAACATTAGCAAGTCTGGTGAAATCACGGTCGCACTGAATGATACC GAAACCACGCCGGCTGACAAAAAGACCGGCGAATGGAAAAGTGACACC TCCACGCTGACCATTTCAAAGAACTCGCAGAAACCGAAGCAACTGGTC TTCACCAAAGAATGCACGATCACCGTGCAGAACTATAATCGTGCCGGT AATGCTCTGGAAGGCTCCCCGGCTGAAATCAAGGACCTGGCGGAACTG AAGGCGGCACTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:131 S6D4-S5D1_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype4andOspAserotype 5withdisulfidebondtype1,LN1peptidelinker (SEQIDNO:184) FNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTGKWDSKT STLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEITTLKEL KNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRANGTRLEY TDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLSKNISKS GEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVFTKEDTI TVQNYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:132 Lip-S6D4-S5D1_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype6 withdisulfidebondtype4andOspAserotype5 withdisulfidebondtype1,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGTGAA AAAACGATTGTTCGCGCCTGTGGCACCCGCCTGGAATACACGGATATC AAGTCGGATGGTTCGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG GAAGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGACAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAATGCACGATCACCGTT CAACGCTATGATAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCTCAGAAAAAACCATCGTCCGCGCT AACGGCACCCGCCTGGAATACACCGACATCAAATCAGACAAGACCGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCTGCGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGATTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAAGATACGATCACCGTGCAAAACTATGACAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAA SEQIDNO:133 Lip-S6D4-S5D1_His_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype4andOspAserotype 5withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEI TTLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAN GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKEDTITVQNYDSAGTNLEGKAVEITTLKELCNALKGLEHHHHHH SEQIDNO:134 Lip-S6D4-S5D1_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype6withdisulfidebondtype 4andOspAserotype5withdisulfidebondtype 1,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGTGAA AAAACGATTGTTCGCGCCTGTGGCACCCGCCTGGAATACACGGATATC AAGTCGGATGGTTCGGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG GAAGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGACAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAATGCACGATCACCGTT CAACGCTATGATAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGAAGAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCTCAGAAAAAACCATCGTCCGCGCT AACGGCACCCGCCTGGAATACACCGACATCAAATCAGACAAGACCGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCTGCGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGATTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAAGATACGATCACCGTGCAAAACTATGACAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG TGTAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:135 S6D1-S5D4_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype1andOspAserotype 5withdisulfidebondtype4,LN1peptidelinker (SEQIDNO:184) FNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTLEGTLAA DGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTGKWDSKT STLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEITTLKEL CNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRACGTRLEY TDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLSKNISKS GEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVFTKECTI TVQNYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:136 Lip-S6D1-S5D4_nt Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype6 withdisulfidebondtype1andOspAserotype5 withdisulfidebondtype4,E.colilpp lipidationsignal,N-terminalCSSforaddition oflipids,LN1peptidelinker(SEQIDNO:184) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGCGAA AAGACCATCGTGCGTGCGAACGGTACCCGCCTGGAATATACGGACATT AAATCGGACGGCAGCGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG TGCGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGATAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAAGATACGATCACCGTT CAACGCTATGACAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCAGTGAAAAAACCATTGTGCGTGCG TGTGGCACCCGTCTGGAATATACCGACATCAAGAGCGATAAAACGGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCGAAGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGACTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAATGCACGATCACCGTGCAAAACTATGATAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAA SEQIDNO:137 Lip-S6D1-S5D4_His_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype1andOspAserotype 5withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation,C- terminalHistag(GLEHHHHHH)(SEQIDNO:214) LipCSSFNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEI TTLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAC GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKECTITVQNYDSAGTNLEGKAVEITTLKELKNALKGLEHHHHHH SEQIDNO:138 Lip-S6D1-S5D4_His_nt Codingsequenceforheterodimerfusionprotein ofOspAserotype6withdisulfidebondtype 1andOspAserotype5withdisulfidebondtype 4,E.colilpplipidationsignal,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),C-terminalHistag (GLEHHHHHH)(SEQIDNO:214) ATGAAAGCTACTAAACTGGTACTGGGCGCGGTAATCCTGGGTTCTACT CTGCTGGCAGGTTGCTCAAGCTTCAACGGCAAAGGTGAAACGAGCGAA AAGACCATCGTGCGTGCGAACGGTACCCGCCTGGAATATACGGACATT AAATCGGACGGCAGCGGCAAAGCAAAGGAAGTCCTGAAAGATTTTACG CTGGAAGGTACCCTGGCAGCAGACGGTAAAACCACGCTGAAGGTGACG TGCGGCACCGTGGTTCTGTCAAAAAACATTCTGAAGTCGGGTGAAATC ACCGCAGCTCTGGATGACAGCGATACCACGCGTGCTACGAAAAAGACC GGTAAATGGGATAGCAAGACCTCTACGCTGACCATTAGTGTCAACTCC CAGAAAACGAAGAATCTGGTGTTCACCAAAGAAGATACGATCACCGTT CAACGCTATGACAGTGCGGGCACCAACCTGGAAGGCAAAGCCGTTGAA ATTACCACGCTGAAAGAACTGTGTAATGCTCTGAAAGGTACTAGTGAC AAAAACAATGGCTCTGGTAGCAAAGAGAAAAACAAAGATGGCAAGTAC TCATTCAACGAAAAAGGCGAAATCAGTGAAAAAACCATTGTGCGTGCG TGTGGCACCCGTCTGGAATATACCGACATCAAGAGCGATAAAACGGGT AAAGCGAAGGAAGTTCTGAAAGATTTTACGCTGGAAGGTACCCTGGCA GCAGACGGTAAAACCACGCTGAAGGTGACCGAAGGTACCGTTACGCTG TCCAAAAACATTAGTAAGTCCGGCGAAATCACGGTCGCCCTGGATGAC ACCGATAGCTCTGGCAACAAAAAGAGCGGTACCTGGGACTCAGGCACC TCGACGCTGACCATTTCTAAAAATCGTACGAAAACCAAGCAGCTGGTC TTCACGAAAGAATGCACGATCACCGTGCAAAACTATGATAGCGCAGGT ACCAATCTGGAAGGCAAAGCTGTGGAAATTACCACGCTGAAAGAACTG AAGAATGCTCTGAAAGGTCTCGAGCACCACCACCACCACCAC SEQIDNO:139 N-palmitoyl-S-(2RS)-2,3-bis-(palmitoyloxy) propylcysteinePam.sub.3C SEQIDNO:140 Lip-S2D0-His aminoacidsofpositions131-273ofBorrelia afzeliistrainK78,OspAserotype2,wild-type sequence,N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:141 Lip-S2D1-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype1(aa182 and269),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LCNALKGLEHHHHHH SEQIDNO:142 Lip-S2D2-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype2(aa182 and272),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNACKGLEHHHHHH SEQIDNO:143 Lip-S2D3-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype3(aa244 and259),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTICVQKYDSAGTNLEGTCVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:144 Lip-S2D4-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype4(aa141 and241),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:145 Lip-S2D5-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype5(aa165 and265),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNCTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTCDE LKNALKGLEHHHHHH SEQIDNO:146 Lip-S2D6-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype6(aa 185and272),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTCTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNACKGLEHHHHHH SEQIDNO:147 Lip-S2D7-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype7(aa199 and223),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTCALNDTNTTQATKKTGAWDSK TSTCTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:148 Lip-S2D8-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype8(aa243 and262),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTCTVQKYDSAGTNLEGTAVECKTLDE LKNALKGLEHHHHHH SEQIDNO:149 Lip-S2D9-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype9(aa184 and204),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGCVTLSKEIAKSGEVTVALNDCNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:150 Lip-S2D10-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype10(aa 201and214),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVACNDTNTTQATKKTCAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:151 Lip-S2D11-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype11(aa 246and259),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVCKYDSAGTNLEGTCVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:152 Lip-S2D12-His aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype12(aa 167and178),N-terminalCKQNforadditionof lipids,C-terminalHistag(GLEHHHHHH) (SEQIDNO:214) LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTCEGKV ANDKVTCEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALKGLEHHHHHH SEQIDNO:153 Lip-S2D0 aminoacidsofpositions131-273ofBorrelia afzeliistrainK78,OspAserotype2,wild-type sequence,N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:154 Lip-S2D1 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype1(aa182 and269),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LCNALK SEQIDNO:155 Lip-S2D2 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype2(aa182 and272),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNACK SEQIDNO:156 Lip-S2D3 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype3(aa244 and259),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTICVQKYDSAGTNLEGTCVEIKTLDE LKNALK SEQIDNO:157 Lip-S2D4 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype4(aa141 and241),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:158 Lip-S2D5 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype5(aa165 and265),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNCTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTCDE LKNALK SEQIDNO:159 Lip-S2D6 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype6(aa185 and272),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTCTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNACK SEQIDNO:160 Lip-S2D7 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype7(aa199 and223),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTCALNDTNTTQATKKTGAWDSK TSTCTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:161 Lip-S2D8 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype8(aa243 and262),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTCTVQKYDSAGTNLEGTAVECKTLDE LKNALK SEQIDNO:162 Lip-S2D9 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype9(aa184 and204),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGCVTLSKEIAKSGEVTVALNDCNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:163 Lip-S2D10 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype10(aa201 and214),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVACNDTNTTQATKKTCAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:164 Lip-S2D11 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype11(aa246 and259),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKV ANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVCKYDSAGTNLEGTCVEIKTLDE LKNALK SEQIDNO:165 Lip-S2D12 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype12(aa167 and178),N-terminalCKQNforadditionoflipids LipCKQNELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTCEGKV ANDKVTCEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSK TSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDE LKNALK SEQIDNO:166 S2D0 aminoacidsofpositions131-273ofBorrelia afzeliistrainK78,OspAserotype2,wild-type sequence ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:167 S2D1 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype1(aa182 and269) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALK SEQIDNO:168 S2D2 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype2(aa182 and272) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNACK SEQIDNO:169 S2D3 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype3(aa244 and259) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTICVQKYDSAGTNLEGTCVEIKTLDELKNALK SEQIDNO:170 S2D4 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype4(aa141 and241) ELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:171 S2D5 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype5(aa165 and265) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNCTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTCDELKNALK SEQIDNO:172 S2D6 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype6(aa 185and272) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTCTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNACK SEQIDNO:173 S2D7 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype7(aa199 and223) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTCALNDTNTTQATKKTGAWDSKTSTCTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:174 S2D8 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype8(aa243 and262) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTCTVQKYDSAGTNLEGTAVECKTLDELKNALK SEQIDNO:175 S2D9 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype9(aa184 and204) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGCVTLSKEIAKSGEVTVALNDCNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:176 S2D10 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype10(aa 201and214) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVACNDTNTTQATKKTCAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:177 S2D11 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype11(aa 246and259) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTL EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVCKYDSAGTNLEGTCVEIKTLDELKNALK SEQIDNO:178 S2D12 aa131-273ofBorreliaafzeliistrainK78,OspA serotype2withdisulfidebondtype12(aa 167and178) ELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTCEGKVANDKVTC EVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTIS VNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:179 B.burgdorferis.s.(strainB31,serotype1), OspA_aa126-273withreplacedhLFA-like sequencefromserotype1OspA FNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTLEGKVAN DKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAAWNSGTS TLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEITKLDEIK NALK SEQIDNO:180 B.garinii(strainPBr,serotype3),OspA_aa 126-274 FNDKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFALEGTLTD GGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTGEWKSDT STLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEIKDLAEL KAALK SEQIDNO:181 B.bavariensis(strainPBi,serotype4),OspA_aa 126-273 FNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFALEGTLAA DKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGKWDSNTS TLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIKTLDELK NALK SEQIDNO:182 B.garinii(strainPHei,serotype5),OspA_aa 126-273 FNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGTWDSGTS TLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEITTLKELK NALK SEQIDNO:183 B.garinii(strainDK29,serotype6),OspA_aa 126-274 FNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTLEGTLAA DGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTGKWDSKT STLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEITTLKEL KNALK SEQIDNO:184 LN1peptidelinkerconstructedfromtwoseparate loopregionsoftheN-terminalhalfofOspA fromB.burgdorferis.s.strainB31(aa65-74 andaa42-53,aminoacidexchangeat position53:D53S) GTSDKNNGSGSKEKNKDGKYS SEQIDNO:185 Lip-S1D4-S2D4_aa HeterodimerfusionproteinofOspAserotypes1 and2bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),aa164-174of OspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18) LipCSSFNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEIT KLDEIKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:186 Lip-S1D1-S2D1_aa HeterodimerfusionproteinofOspAserotype1 andOspAserotype2withdisulfidebondtype 1,N-terminalCSSforadditionoflipids,LN1 peptidelinker(SEQIDNO:184),aa164-174 ofOspAserotype1replacedbynon-hLFA-1-like sequenceNFTLEGKVAND(SEQIDNO:18), N-terminallipidation LipCSSFNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEIT KLDEICNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALK SEQIDNO:187 Lip-S3D4-S4D4_aa HeterodimerfusionproteinofOspAserotype3 andOspAserotype4withdisulfidebondtype 4,N-terminalCSSforadditionoflipids, LN1peptidelinker(SEQIDNO:184), N-terminallipidation LipCSSFNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEI KDLAELKAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAC GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKECTITVQKYDSAGTNLEGNAVEIKTLDELKNALK SEQIDNO:188 Lip-S3D1-S4D1_aa HeterodimerfusionproteinofOspAserotypes3 and4bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEI KDLAELCAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAN GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKEDTITVQKYDSAGTNLEGNAVEIKTLDELCNALK SEQIDNO:189 Lip-S5D4-S6D4_aa HeterodimerfusionproteinOspAserotypes5and 6bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEIT TLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKECTITVQRYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:190 Lip-S5D1-S6D1_aa HeterodimerfusionproteinofOspAserotypes6 bothwithdisulfidebondtype1,N-terminal CSSforadditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEIT TLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKEDTITVQRYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:191 Lip-S2D4-S1D4_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18), N-terminallipidation LipCSSFNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KECTITVQQYDSNGTKLEGSAVEITKLDEIKNALK SEQIDNO:192 Lip-S2D1-S1D1_aa HeterodimerfusionproteinofOspAserotypes2 and1bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),aa164-174ofOspA serotype1replacedbynon-hLFA-1-likesequence NFTLEGKVAND(SEQIDNO:18), N-terminallipidation LipCSSFNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KENTITVQQYDSNGTKLEGSAVEITKLDEICNALK SEQIDNO:193 Lip-S4D4-S3D4_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKECTITVQNYNRAGNALEGSPAEIKDLAELKAALK SEQIDNO:194 Lip-S4D1-S3D1_aa HeterodimerfusionproteinofOspAserotypes4 and3bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKENTITVQNYNRAGNALEGSPAEIKDLAELCAALK SEQIDNO:195 Lip-S6D4-S5D4_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype4,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEI TTLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAC GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKECTITVQNYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:196 Lip-S6D1-S5D1_aa HeterodimerfusionproteinofOspAserotypes6 and5bothwithdisulfidebondtype1,N- terminalCSSforadditionoflipids,LN1peptide linker(SEQIDNO:184),N-terminallipidation LipCSSFNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEI TTLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAN GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKEDTITVQNYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:197 Lip-S1D4-S2D1_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype4andOspAserotype 2withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation LipCSSFNEKGEVSEKIITRACGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKEGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKECTITVQQYDSNGTKLEGSAVEIT KLDEIKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRENG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKCGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQDTITVQKYDSAGTNLEGTAVEIKTLDELCNALK SEQIDNO:198 Lip-S1D1-S2D4_aa HeterodimerfusionproteinofOspAserotype1 withdisulfidebondtype1andOspAserotype 2withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation LipCSSFNEKGEVSEKIITRADGTRLEYTGIKSDGSGKAKEVLKNFTL EGKVANDKTTLVVKCGTVTLSKNISKSGEVSVELNDTDSSAATKKTAA WNSGTSTLTITVNSKKTKDLVFTKENTITVQQYDSNGTKLEGSAVEIT KLDEICNALKGTSDKNNGSGSKEKNKDGKYSFNEKGELSAKTMTRECG TKLEYTEMKSDGTGKAKEVLKNFTLEGKVANDKVTLEVKEGTVTLSKE IAKSGEVTVALNDTNTTQATKKTGAWDSKTSTLTISVNSKKTTQLVFT KQCTITVQKYDSAGTNLEGTAVEIKTLDELKNALK SEQIDNO:199 Lip-S3D4-S4D1_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype4andOspAserotype 4withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNEKGKLSEKVVTRACGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTEGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKECTITVQNYNRAGNALEGSPAEI KDLAELKAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAN GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTCGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKEDTITVQKYDSAGTNLEGNAVEIKTLDELCNALK SEQIDNO:200 Lip-S3D1-S4D4_aa HeterodimerfusionproteinofOspAserotype3 withdisulfidebondtype1andOspAserotype 4withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNEKGKLSEKVVTRANGTRLEYTEIKNDGSGKAKEVLKGFAL EGTLTDGGETKLTVTCGTVTLSKNISKSGEITVALNDTETTPADKKTG EWKSDTSTLTISKNSQKPKQLVFTKENTITVQNYNRAGNALEGSPAEI KDLAELCAALKGTSDKNNGSGSKEKNKDGKYSFNAKGELSEKTILRAC GTRLEYTEIKSDGTGKAKEVLKDFALEGTLAADKTTLKVTEGTVVLSK HIPNSGEITVELNDSNSTQATKKTGKWDSNTSTLTISVNSKKTKNIVF TKECTITVQKYDSAGTNLEGNAVEIKTLDELKNALK SEQIDNO:201 Lip-S5D4-S6D1_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype4andOspAserotype 6withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNEKGEISEKTIVRACGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKECTITVQNYDSAGTNLEGKAVEIT TLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRANG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKEDTITVQRYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:202 Lip-S5D1-S6D4_aa HeterodimerfusionproteinofOspAserotype5 withdisulfidebondtype1andOspAserotype 6withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNEKGEISEKTIVRANGTRLEYTDIKSDKTGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVTLSKNISKSGEITVALDDTDSSGNKKSGT WDSGTSTLTISKNRTKTKQLVFTKEDTITVQNYDSAGTNLEGKAVEIT TLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNGKGETSEKTIVRACG TRLEYTDIKSDGSGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVVLSK NILKSGEITAALDDSDTTRATKKTGKWDSKTSTLTISVNSQKTKNLVF TKECTITVQRYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:203 Lip-S2D4-S1D1_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype4andOspAserotype 1withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation LipCSSFNEKGELSAKTMTRECGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQCTITVQKYDSAGTNLEGTAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRADG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKCGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KENTITVQQYDSNGTKLEGSAVEITKLDEICNALK SEQIDNO:204 Lip-S2D1-S1D4_aa HeterodimerfusionproteinofOspAserotype2 withdisulfidebondtype1andOspAserotype 1withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),aa164-174ofOspAserotype1 replacedbynon-hLFA-1-likesequenceNFTLEGKVAND (SEQIDNO:18),N-terminallipidation LipCSSFNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKEVLKNFTL EGKVANDKVTLEVKCGTVTLSKEIAKSGEVTVALNDTNTTQATKKTGA WDSKTSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLEGTAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEVSEKIITRACG TRLEYTGIKSDGSGKAKEVLKNFTLEGKVANDKTTLVVKEGTVTLSKN ISKSGEVSVELNDTDSSAATKKTAAWNSGTSTLTITVNSKKTKDLVFT KECTITVQQYDSNGTKLEGSAVEITKLDEIKNALK SEQIDNO:205 Lip-S4D4-S3D1_aa HeterodimerfusionproteinofOspAserotype4 withdisulfidebondtype4andOspAserotype 3withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNAKGELSEKTILRACGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTEGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKECTITVQKYDSAGTNLEGNAVEIK TLDELKNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRANG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTCGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKENTITVQNYNRAGNALEGSPAEIKDLAELCAALK SEQIDNO:206 Lip-S4D1-S3D4_aa Codingsequenceforintermediateandfinal heterodimerfusionproteinsofOspAserotype4 withdisulfidebondtype1andOspAserotype3 withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNAKGELSEKTILRANGTRLEYTEIKSDGTGKAKEVLKDFAL EGTLAADKTTLKVTCGTVVLSKHIPNSGEITVELNDSNSTQATKKTGK WDSNTSTLTISVNSKKTKNIVFTKEDTITVQKYDSAGTNLEGNAVEIK TLDELCNALKGTSDKNNGSGSKEKNKDGKYSFNDKGKLSEKVVTRACG TRLEYTEIKNDGSGKAKEVLKGFALEGTLTDGGETKLTVTEGTVTLSK NISKSGEITVALNDTETTPADKKTGEWKSDTSTLTISKNSQKPKQLVF TKECTITVQNYNRAGNALEGSPAEIKDLAELKAALK SEQIDNO:207 Lip-S6D4-S5D1_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype4andOspAserotype 5withdisulfidebondtype1,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNGKGETSEKTIVRACGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTEGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKECTITVQRYDSAGTNLEGKAVEI TTLKELKNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAN GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTCGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKEDTITVQNYDSAGTNLEGKAVEITTLKELCNALK SEQIDNO:208 Lip-S6D1-S5D4_aa HeterodimerfusionproteinofOspAserotype6 withdisulfidebondtype1andOspAserotype 5withdisulfidebondtype4,N-terminalCSS foradditionoflipids,LN1peptidelinker (SEQIDNO:184),N-terminallipidation LipCSSFNGKGETSEKTIVRANGTRLEYTDIKSDGSGKAKEVLKDFTL EGTLAADGKTTLKVTCGTVVLSKNILKSGEITAALDDSDTTRATKKTG KWDSKTSTLTISVNSQKTKNLVFTKEDTITVQRYDSAGTNLEGKAVEI TTLKELCNALKGTSDKNNGSGSKEKNKDGKYSFNEKGEISEKTIVRAC GTRLEYTDIKSDKTGKAKEVLKDFTLEGTLAADGKTTLKVTEGTVTLS KNISKSGEITVALDDTDSSGNKKSGTWDSGTSTLTISKNRTKTKQLVF TKECTITVQNYDSAGTNLEGKAVEITTLKELKNALK SEQIDNO:209 B.afzelii(strainK78;OspAserotype2) aa17-273,lipidationsignalsequenceremoved (aa1-16:MKKYLLGIGLILALIA,(SEQIDNO:14)), C-terminalHistag(GLEHHHHHH)(SEQIDNO:214) CKQNVSSLDEKNSASVDLPGEMKVLVSKEKDKDGKYSLKATVDKIELK GTSDKDNGSGVLEGTKDDKSKAKLTIADDLSKTTFELFKEDGKTLVSR KVSSKDKTSTDEMFNEKGELSAKTMTRENGTKLEYTEMKSDGTGKAKE VLKNFTLEGKVANDKVTLEVKEGTVTLSKEIAKSGEVTVALNDTNTTQ ATKKTGAWDSKTSTLTISVNSKKTTQLVFTKQDTITVQKYDSAGTNLE GTAVEIKTLDELKNALKGLEHHHHHH SEQIDNO:210 Cysteine-containingpeptidefromE.coli CSS SEQIDNO:211 Cysteine-containingpeptidefromOspA CKQN SEQIDNO:212 aminoacidsofpositions126-274ofB.garinii strainT25,OspAserotype7 FNDKGKLSEKVVTRANGTRLEYTEIQNDGSGKAKEVLKSLTLEGTLTA DGETKLTVEAGTVTLSKNISESGEITVELKDTETTPADKKSGTWDSKT STLTISKNSQKTKQLVFTKENTITVQKYNTAGTKLEGSPAEIKDLEAL KAALK SEQIDNO:213 ForwardoligonucleotideprimerfortherecAgene ofallrelevantBorreliaspeciescausingLyme borreliosis CATGCTCTTGATCCTGTTTA SEQIDNO:214 C-terminalHistag GLEHHHHHH SEQIDNO:215 ReverseoligonucleotideprimerfortherecAgene ofallrelevantBorreliaspeciescausing Lymeborreliosis CCCATTTCTCCATCTATCTC

[0327] The entire contents of all of the references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated by reference.