COMPLEXES OF CYTOMEGALOVIRUS PROTEINS
20220106364 · 2022-04-07
Inventors
Cpc classification
C12N7/00
CHEMISTRY; METALLURGY
C12N2710/16134
CHEMISTRY; METALLURGY
A61K2039/55555
HUMAN NECESSITIES
C12N2710/16122
CHEMISTRY; METALLURGY
A61P43/00
HUMAN NECESSITIES
C12N2710/16151
CHEMISTRY; METALLURGY
International classification
Abstract
An isolated human cytomegalovirus (HCMV) membrane protein complex that comprises gH, gL and at least one more HCMV glycoprotein is provided. In some embodiments the complex consists of gH, gL and gO. In other embodiments the complex consists of gH, gL, pUL128, pUL130 and pUL131A. Processes for expressing and purifying such complexes, and subsequent uses of such complexes in immunogenic compositions and vaccines, are also provided.
Claims
1. A process for producing an isolated HCMV membrane protein complex comprising gH, gL and at least one additional HCMV glycoprotein, wherein said process comprises recombinant expression of said gH, gL and at least one more HCMV glycoprotein.
2. A process for expressing an HCMV membrane protein complex comprising gH, gL and at least one more HCMV glycoprotein by: introducing one or more recombinant nucleic acid molecules which encode gH, gL and at least one more HCMV glycoprotein into an expression system, expressing said one or more nucleic acids in said expression system; and purifying said membrane protein complex.
3. The process of claim 2, which comprises the step o f transfecting mammalian cells with a fast nucleic acid construct which encodes a fragment of gH that lacks the transmembrane domain, a second nucleic acid construct which encodes the gL protein; and a third nucleic acid construct which encodes at feast one more HCMV glycoprotein.
4. The process of any preceding claim, wherein the HCMV membrane protein complex consists of gH, gL and gO.
5. The process of any preceding claim, wherein the HCMV membrane protein complex consists of gH, gL, pUL128, pUL130 and pUL131A.
6. The process of claim 5, wherein said: pUL128 comprises or consists of any one of the sequences recited in SEQ ID NOs: 13, 14, 15 or 33; pUL130 comprises or consists of any one of the sequences recited in SEQ ID NOs: 16, 17 or 34, and/or pUL131A comprises or consists of any one of the sequences recited in SEQ ID NOs: 18, 19, 20 or 35.
7. The process of any preceding claim, wherein the HCMV membrane protein complex has a purity of >85%, >86%, >87%, >88%, >89%, >90%, >91%, >92%, >93%, >94% of >95% by mass.
8. The process of any preceding claim, wherein one or more of gH, gL, gO, pUL128, pUL130 and pUL131A in said HCMV membrane protein complex: have a mammalian glycosylation pattern; and/or do not contain an insect cell pattern of glycosylation.
9. A purified HCMV membrane protein complex comprising gH, gL and at least one more HCMV glycoprotein.
10. An HCMV membrane protein complex comprising gH, gL and at least one more HCMV glycoprotein, w herein said complex is produced by the process of any preceding claim.
11. An immunogenic composition comprising die isolated HCMV membrane complex of claim 9 or claim 10.
12. The immunogenic composition of claims 11, wherein said composition is a vaccine.
13. The immunogenic composition of claim 11, wherein said composition comprises an adjuvant.
14. The immunogenic composition of claim 12, wherein said adjuvant is an oil-in-water emulsion or an aluminium salt.
15. An immunogenic composition comprising: a self-replicating RNA molecule that encodes an HCMV membrane protein complex; and the HCMV membrane protein complex of claim 9 or claim 10.
16. A kit comprising: a priming composition comprising a self-replicating RNA molecule that encodes an HCMV membrane protein complex; and a boosting composition comprising the HCMV membrane protein complex of claim 9 or claim 10.
17. A recombinant nucleic acid molecule which encodes gL, gH that lacks a transmembrane domain, and at least one additional HCMV glycoprotein, wherein said recombinant nucleic acid: (a) is not a self-replicating RNA molecule; (b) is not an alphavirus replicon; (c) does not encode any alphavirus nonstructural proteins, such as NSP1, NSP2, NSP3 and NSP4; (d) does not contain; an Internal Ribosomal Entry Site (IRES), such as EMCV or EV71; and/or (e) does not contain a viral 2A site, such as FMDV.
18. The recombinant nucleic acid molecule of claim 17, wherein said recombinant nucleic acid molecule encodes: gL, gH that lacks a transmembrane domain, pUL128, pUL130 and pUL131A; or gL, gH that lacks a transmembrane domain and gO.
19. A plurality of recombinant nucleic acids, wherein said plurality of recombinant nucleic acids encode gL, gH that lacks a transmembrane domain, and at least one additional HCMV glycoprotein, wherein one or more or all of said plurality of recombinant nucleic acids: (a) is not a self-replicating RNA molecule; (b) is not an alphavirus replicon; (c) does not encode any alphavirus nonstructural proteins, such as NSP1, NSP2, NSP3 and NSP4; (d) does not contain: an Internal Ribosomal Entry Site (IRES), such as EMCV or BV71; and/or (c) does not contain a viral 2A site, such as FMDV.
20. The plurality of recombinant nucleic acids of claim 19 comprising: a first construct encoding gH that lacks a transmembrane domain and gL; and a second construct encoding one additional HCMV glycoprotein.
21. The plurality of recombinant nucleic acids of claim 20, wherein said second construct encodes: pUL128, pUL130 and pUL131A; or g.
22. The plurality of recombinant nucleic acids of claim 21 comprising: a first recombinant nucleic acid molecule which encodes gL; a second recombinant nucleic acid molecule which encodes a fragment of gH that lacks a transmembrane domain; and one or more third recombinant nucleic acid molecules which encode one or more additional HCMV proteins.
23. A cell comprising gH, gL and al least, one additional HCMV glycoprotein, wherein said cell docs not: (a) contain the HCMV genome; (b) produce HCMV virions; (c) contain self-replicating RNA molecules encoding said gH, gL and at least one additional HCMV glycoprotein; and/or (d) contain alphavirus replicons.
24. A process for producing an isolated or a purified HCMV membrane protein complex comprising gH, gL and at least one additional HCMV glycoprotein, wherein said process involves growing the cell of claim 23 in growth medium.
25. The process of claim 24, whereto said HCMV membrane protein complex is secreted into said growth medium.
26. The process of claim 25, wherein sad HCMV membrane protein complex accumulates to a concern ration of >0.8 mg, >0.85 mg, >0.88 mg, >0.9 mg, >0.95 mg, >1 mg, >1.5 mg, >2 mg, >2.5 mg, >3 mg, >3.5 mg, >4 mg, >4.5 mg, >5 mg of complex per lure of growth medium.
27. An RNA prime-protein boost regimen comprising: performing one or more priming immunization(s) with RNA that encodes one or more of the protein components of an HCMV membrane protein complex, wherein said HCMV membrane protein complex comprises gH, gL and at least one additional HCMV glycoprotein, performing one or more boosting immunization(s) later with a purified HCMV membrane protein complex, wherein sad purified HCMV membrane protein complex comprises gH, gL and at least one additional HCMV glycoprotein.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
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EXAMPLES
Example 1—Immunogenicity of Replicons Expressing Pentameric Complex
[0213] In WO 2012/051211, an alphavirus replicon vector expressing all five proteins of the pentameric complex (gH, gL, pUL128, pUL130 and pUL131A) from a single construct was produced. The RNAs expressed by this vector were either packaged into VRPs or formulated for RNA vaccination either b complexing replicons with CNEs o by encapsulating, replicons in LNPs. The VRPs and formulated RNAs were used to immunize BALB/c mice at three-week intervals. Sera from immunized mice were used in microneutralization assays to block infection of epithelial cells with HCMV TB40 (in the absence of complement). The HCMV TB40 strain is similar to clinical strains and infects endothelial and epithelial cells, natural target cells of HCMV in vivo (17). Microneutralization assay data demonstrated that replicons expressing the pentameric complex elicited more potently neutralizing antibodies than replicons expressing Microneutralisation data also showed that antibodies elicited by RNA expressing pentameric complex are able to neutralize HCMV infection in epithelial cells (because they tart et the pentameric complex), but not in fibroblasts (in which infection does not .require the pentameric complex), thus demonstrating that RNA expressing the pentameric complex elicits antibodies that specifically target the intact pentameric complex rather than a gH/gL dimer. This work demonstrates that antibodies can be raised against the pentameric complex, and those antibodies are capable of neutralizing HCMV infection.
Example 2—Constructs for Stable Expression of the Pentameric Complex in Mammalian Cells
[0214] Five nucleic acid constructs were produced to enable to expression and purification of the pentameric complex mammalian cells. Previous attempts to purify the pentameric complex when constructs including the gene encoding the full-length gH protein were unsuccessful. In an attempt to overcome this problem, the inventors produced constructs that encode only the ectodomain of gH (gHecto) with a C-terminal myc-(His)6 tag (SEQ ID NO: 6) rather than the full-length sequence. The following five constructs were used to produce the pentameric complex: a construct encoding SEQ ID NO: 6 (
Example 3—Protocol for Transfection and Expression of Protein Complexes in 293-6E Cells
Materials:
[0215] Mammalian 293-6E Cells (Gibco Freestyle 293 Expression Medium; Opti-MEM and Polyethylenimine Linear (PEI), MW 25,000.
Preparation of Cells
[0216] 293-6E cells were mainlined in scrum-free 293 Expression Medium Once the cells are doubling every 24 hours and at more than 90% viability, the cells were diluted to a density of 1×10.sup.6/1 mL media.
Transfection
[0217] DNA corresponding to each construct was diluted in Opti-MEM using a volume of Opti-MEM that is 2.5% of the volume of cell culture to be transfected DNA constructs were combined in an appropriate ratio such that total DNA was equal to 1 μg/1 mL culture volume. For example, for the stable expression of the pentameric complex using 1 L cell culture, 200 μg of each of SEQ ID NOs: 23-27 were added to 25 mL Opti-MEM.
[0218] PEI was diluted m Opti-MEM using a volume of Opti-MEM that is 2.5% the volume of cell culture to be transfected. The diluted PEI was incubated for 5 min at room temperature with occasional swirling to mix. 3 μg PEI was used per 1 ml. culture (e.g., for IL cell culture 3 mg PEI was diluted in 25 mL Opti-MEM).
[0219] The DNA mix was added to the PEI mix (so that 1 μg total DNA+3 μg PEI were used per 1 mL culture), swirled and incubated at room temperature for 30 min. The DNA-PEI mix was added to cells by gradually adding mixture and swirling cells occasionally such that mixture was added evenly to culture The cells were then immediately returned to the original growth conditions.
Expression and Harvest
[0220] Three days post-transfection, the media was harvested by spinning the cells down at 2,000 rpm. The media was then concentrated approximately 10× and diafiltered into buffer containing 300 mM NaCl, 25 mM Tris gH 7.5. Finally, the dialyzed media was frozen at −8-° C. Fresh media were added to the culture and three more days later the media was harvested and concentrated/diafiltered as above.
Example 4—Protocol for Purification of the HCMV Complexes
Materials
[0221] GE AKTAxpress. Qiagen Ni-NTA Superflow Cartridges, 5 ml: 96 Well Clear V-Bottom 2 mL Polypropylene Block; Buffer A (=binding buffer) 50 mM Tris-HCl pH 7.5, 300 mM NaCl, 5 mM Imidazole: Buffer B (=elution buffer) 50 mM Tns-HCl pH 7.5, 300 mM NaCl, 1 M Imidazole: SEC buffer (=for buffer exchange and size exclusion chromatography); 2×500 ml 0.5 M NaOH solution for system cleaning; Invitrogen NuPAGE® Novex 4-12% Bis-Tris Gel 1.0 mm, 12 well; NuPAGE® LDS Sample Buffer (4×) and NuPAGE® Sample Reducing Agent (10×).
Procedures
[0222] Buffers were prepared with endotoxin-free stock solutions and filtered Milli-Q water.
[0223] The medium to be purified was thawed in a warm water bath. Meanwhile AKTAxpress was cleaned with 0.5M NaOH, to get rid of possible endotoxin contamination as well as residual protein/media, and then rinsed with filtered endotoxin-free Milli-Q water.
[0224] The Ni-NTA super flow cartridge was connected to the A KTAxpress system, and the water and buffers A and B were set in place. The program “Ni-NTA prep” was then started in order to flush the system with buffers, wash away ethanol in the column, and run buffer A through the column to equilibrate it.
[0225] The fraction collecting 96-well was prepared by putting 3.5 μl 500 mM EDTA solution in each well. The loading sample was also prepared immediately before loading. When the medium had thawed 1/500 volume of 2.5M imidazole stock was added, and mixed gently. The loading sample was then set in place.
[0226] The purification program was then started. This program performed the following steps: sample loaded onto the column: washed away the unbound compounds with buffer A until the baseline settles; washed away non-specifically binding compounds with 15 column volumes of 2.5% buffer B (=30 mM Imidazole), elute, the HCMV protein complex with 10 column volumes of 25% buffer B (=254 mM Imidazole); and finally washed the column with 5 column volumes of 100% buffer B (=1 M Imidazole). The sample loading rate was 2.5 ml/min, whereas the wash and elution rate was 5 mL/min. The flow through in whole and 1.75 ml each of fractions from wash and elution were collected).
[0227] Six or seven fractions from the 250 mM Imidazole elution peak were selected to be analysed by SDS-PAGE. The four or five fractions which had the highest amount or protein according to the. SDS-PAGE gel were pooled together, and dialyzed against 2 L SEC buffer the 1 hr at RT, twice. The dialysate was recovered and the concentration measured using the BCA method. The presence of all components of the complex in the purified protein pool was verified by Western blot.
[0228] In order to increase the purity of some samples, size exclusion chromatography (SEC) was performed. On a Superdex 200 10/300 GL (GE Healthcare, 17-5175-01) equilibrated with SEC buffer for more than two column volumes. The dialyzed pool was loaded one column volume of buffer was run through the column, and 1 mL fractions were collected. SDS-PAGE was performed to determine which fractions to pool and keep.
Example 5—Expression, Purification and Characterization of the Trimeric gH/gL/gO Complex
[0229] The following three constructs were produce& gH ectodomain with C-terminal APP tag, full-length gL and full-length gO with a C-terminal (His)6 tag. These three constructs were co-expressed in HEK 293 cells according to the method described in Example 3. The purification method of Example 4, involving a Ni.sup.2+ affinity chromatography, was performed.
[0230] The purified samples were then subjected to SDS-PAGE, followed by Western blot analysis using anti-APPtag (gH) and anti-6His (gO) antibodies. These three antibodies bound to different proteins under reducing conditions (+heat, +DTT), but all bound to a single complex in non-reducing conditions (−heat, −DTT). These results demonstrate the successful purification of gH/gL/gO as a trimeric complex. Approximately 0.5 mg/L media of the complex was purified from HEK 293 cells. SEC increased the purity of the gH/gL/gO complex.
Example 6—Expression and Purification of the Pentameric Complex
[0231] HEK293 cells were co-transfected with the five constructs described in Example 2 according to the method described in Example 3, the media were harvested 3 and 6 days post transfection, and the expressed protein was purified by Ni-NTA chromatography according to the method of Example 4.
[0232] A single peak in the size exclusion chromatogram for the purified pentameric complex (
Example 7—Western Blotting of HCMV Pentameric Complex
Materials
[0233] BioRad Trans-Blot SD Semi-Dry Electrophoretic Transfer Cell; Invitrogen Nitrocellulose membranes, 0.2 μm pore; NuPAGE® Transfer Buffer (20×); Methanol, Odyssey® Blocking Buffer; DPBS; 10× PBS, Primary antibodies; Mouse anti-His tag, rabbit anti-gL 27-46, mouse anti-pUL128 4B10, mouse anti-UL130 3E3, and rabbit anti-UL131A 90-136; secondary antibodies. IRDye 800CW Goat anti-Rabbit IgG (H+L). IRDye 680LT Goat anti-Mouse IgG (H+L).
Procedures
[0234] Three sets of antibodies were used, one for the detection of gHecto-His/gL, one for the detection of pUL128/pUL131A, and one for the detection of pUL130.
[0235] 9 μl of the protein was mixed with 3 μl of LDS sample buffer/reducing agent mixture (9:1) and boiled at 100° C. for 3 minutes. The boiled samples were loaded on the wells and run at 200 V for 35 minutes. The protein w as then transferred to a 0.2 μm nitrocellulose membrane using the Trans-Blot SD Semi-Dry Electrophoretic Transfer Cell at 20 V for 35 minutes. The membrane was blocked with blocking buffer at room temperature for 30 minutes. The membranes were incubated with primary antibody solutions at RT for 1 hr. Primary antibody solutions consisted of: (A) 1:10000 dilution of anti-His tag and 1:5000 dilution of anti-gL, (B) 1:500 dilution of anti-pUL128 and 1:1000 dilution of anti-UL131A, and (C) 1:500 dilution of anti-UL130, all diluted in 1:1 mixture of the blocking buffer and DPBS The membranes were rinsed three times with PBS+0.1% Tween at RT, and then incubated with secondary antibody solutions at RT for 1 hr. For membranes (A) and (B), 1:25000 dilution each of anti-mouse and anti-rabbit antibodies in a 1:1 mixture with the blocking buffer and DPBS was used. For membrane (C), 1:25000 dilution of anti-mouse antibodies were used only. The membranes were rinsed three times with PBS+0.1% Tween at RT, and then rinsed with DPBS once at RT. The membrane was scanned with Odyssey Infrared Imaging System (Li-Cor 9201) and analyzed using Odyssey software version 2.1.12.
[0236] All five members of the pentameric complex: gHecto-His, gL, pUL128, pUL130 and pUL131A were present within the purified complex, were identified by SDS-PAGE and Western blot analysis (
[0237] gHecto-His, gL, and pUL128 co-migrate in an SDS Bis-tris gel without heat nor DTT, but the association of pUL128 and gH/gL completely disappears in the presence of DTT (data not shown), thus demonstrating that pUL128 associates with gH/gL through a disulfide bond. A does not co-migrate with gH/gL/pUL128, indicating that it is incorporated into the pentameric complex by non-covalent bonds.
[0238] The most dominant band on the gels was near the complex position with non-reducing, non-boiling conditions, and was thus thought to correspond to the HCMV pentameric complex. The purity was estimated to be 90%, by mass. With SEC purification the purity increased to nearly 100%. Approximately 0.6 mg of pentameric complex per litre of media could be purified by Ni-NTA purification.
Example8—Recombinant Pentameric Complex Binds to Conformation Dependent Neutralizing Antibodies
[0239] A panel human neutralizing antibodies (HumAb) Were isolated from memory B cells of seropositve individuals. Direct ELISA was performed in which pentameric complex protein was immobilized on a plate and neutralizing antibodies were added in a 10-fold series dilution. The results of this ELISA are shown in Table 1. The HumAb bound to several UL proteins and gH/gL/pUL128/pUL130, which confirmed the correct conformation of the pentameric complex forms. Binding of HumAb against suggests that these epitopes are exposed on the recombinant complex.
TABLE-US-00001 TABLE 1 HuMab 10P3 5A2 4I22 8J16 7I13 15D8 8I21 3G16 11B12 cytotect Chick. Lyso. epitope pUL128/ pUL128/ pUL130/ pUL130/ pUL130/ pUL130/ pUL130/ gH/gL/ pUL131A pUL131A pUL131A pUL131A pUL131A pUL128/ gH/gL gH/gL site 3 site 2 site 1 site 1 site 2 pUL128 pUL130 site A site B KD (nM) 0.17 0.1 0.1 0.13 0.11 0.33 0.57 0.06 0.21 9.8 —
Example 9—Pentameric Complex Elicits Higher Neutralizing Titers Than gH/gL
[0240] 0.1/1 μg purified gH/gL, and 0.16 μg/1.6 μg pentameric complex protein were formulated with or without MF59 and used for immunization or mice. The neutralizing titer of 3wp3 showed approximately a 4-fold increase for pentameric complex compared with gH/gL (which in turn elicits higher neutralizing titers compared with gB) (
Example 10—Production of Monoclonal Antibodies Using Purified gH/gL/gO as an Antigen
[0241] The purified gH/gL/gO complex is diluted to 0.4 mg/mL in 150 mM NaCl, 25 mM Iris (pH 7.5), 1 mM EDTA and frozen. The gH/gL/gO complex is thawed on the day of vaccination and 438 μl of adjuvant is added to the thawed gH/gL/gO complex and mixed well by inverting the tubes at least 10 times. The resulting composition is used within 1 hour of mixing.
[0242] Two groups of three 6-8 week-old female BALB/c mice are immunized with a composition comprising 50 μg purified gH/gL/gO, and MF59 adjuvant. Each mouse is immunized with 125 μL, in each quadriceps muscle (i.e. each mouse received 250 μL) and bled from their orbital sinuses.
[0243] For each group of three mice, the immunization schedule is summarised in Table 2 below:
TABLE-US-00002 TABLE 2 Weeks 0 0 3 5 6 8 Procedure Bleed 0 Immunization 1 Immunization 2 Bleed 2 Immunization 3 Bleed 3
[0244] In order to purify monoclonal antibodies against gH/gL/gO, the gH/gL/gO antigen is used for primary ELISA screening and then the positive clones from the primary screening are then further screened using the gH/gL/gO antigen.
[0245] A similar method can be employed to produce monoclonal antibodies using the purified pentameric complex as an antigen.
Example 11—A SAM™ Vaccine Prime, Protein Boost and Coadministration of RNA and Subunit Using the HCMV Pentameric Antigen
[0246] Mice were immunized three times, three weeks apart with a SAM vaccine, which is a self-replicating RNA as described herein, encoding the HCMV pentameric complex, purified pentameric subunit adjuvanted with MF59, different sequences of SAM vaccine followed by subunit in M59, or a combination of the two (Table 3). The SAM vaccine was encapsulated in synthetic LNPs for non-viral delivery. A group of control mice did not receive any vaccine.
TABLE-US-00003 TABLE 3 No. No. Group Mice Doses Antigen Formulation Dose 1 4 — 3 — 1 2 8 3 SAM vaccine encoding Lipid 1 microgram pentameric complex (Penta nanoparticle SAM vaccine) (LNP) 3 8 3 Purified pentameric complex MF59 1 microgram (Penta subunit) 4 8 3 1st Penta SAM vaccine LNP 1 microgram 2nd and 3rd Penta subunit MF59 5 8 3 1st and 2nd Penta SAM LNP 1 microgram vaccine 3rd Penta subunit MF59 6 8 3 Penta SAM + Penta LNP 1 microgram + subunit (mixed) 1 microgram
[0247] Sera were harvested three weeks after each immunization and used for ELISA to determine binding antibody titers, using the same purified antigen in the assay as in the subunit vaccine. The sera were also used for HCMV microneutralization assay using TB40 of VR1814 infection of ARPE-19 epithelial cells. Three or four weeks after the third immunization, spleens were extracted from sacrificed mice. Spleen cells were stimulated in vitro with purified protein or a pool of 15-mer peptides (overlapping by 11 amino acids) corresponding to the c-terminal half of the gH protein, stained for cytokine expression, and analyzed using flow cytometry.
[0248] SAM vaccine and subunit/MF59 alone elicited potently neutralizing antibody responses after three doses (
[0249] Two doses of SAM vaccine followed by a single dose of subunit/MF59 did not appear to benefit neutralizing responses compared to either subunit/MF or SAM vaccine alone. Mixing SAM vaccine with subunit, without MF59, elicited a strong response after the first dose, similar to RNA alone, and elicited strong neutralizing titers after two and three doses.
[0250] CD4+ T cell responses to the vaccinations using purified gH/gL and pentameric subunits were analyzed. SAM vaccine prime protein boost and mixed SAM vaccine+subunit elicited more CD4+ TI cells responding to gH/gL re-stimulation than SAM vaccine or subunit/MF59 alone (
[0251] CD8+ T cell responses to the vaccinations using purified pentameric subunit or a pool of peptides to gH were also analyzed. The only significant CD8 responses seen when re-stimulating with pentameric subunit was in the mice immunized with two doses of SAM vaccine followed by one dose of subunit/MF59 (
[0252] Conclusions: One dose of SAM vaccine followed b two doses of subunit/MF59as well as SAM vaccine+subunit, elicited higher neutralizing titers than subunit/MF59 alone. The response to SAM vaccine+subunit did not require addition of MF59 adjuvant. The largest impact of SAM Vaccine prime subunit/MF59 boost was on cellular immune responses. Any combination including the SAM vaccines. produced primarily a Th1/Th0 CD4+ response. Moreover, two immunizations with SAM vaccine followed by one immunization with subunit/MF59 produced the strongest CD8+ responses. This study shows that a SAM vaccine prime protein boost regimen can be optimized to produce a desired immune response, i.e. cellular or humoral.
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TABLE-US-00004 SEQUENCE LISTING (gH from HCMV strain Merlin = GI:52139248) SEQ ID NO: 1 MRPGLPSYLIILAVCLFSHLLSSRYGAEAVSEPLDKAFHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAIS FNFFQSYNQYYVFHMPRCLFAGPLAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQLKAQDSLGEQPTT VPPPIDLSIPHVWMPPQTTPHGWTESHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTE DFFVVTVSIDDDTPMLLIFGHLPRVLFKAPYQPDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLD LASLLRNSFHRYAVLVLKSGRCQMLDRRTVEMAFAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITCLS QTPPRTTLLLYPTAVDLAKRALWTPNQITDITSLVRLVYILSKQNQQHLIPQWALRQIADFALKLGKTHLASFLSAF ARQELYLMGSLVHSMLVHTTERREIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDHSLERLTRLF PDATVPATVPAALSILSTMQPSTLETFPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVSTTVVGQSLIIT QTDSQTKCELTRNMHTTHSITVALNISLENCAFCQSALLEYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTH YLMLLKNGTVLEVTDVVVDTDSRLLMMSVYALSAIIGIYLLYRMLKTC (gH from HCMV strain Towne = GI:138314) SEQ ID NO: 2 MRPGLPSYLIVLAVCLLSHLLSSRYGAEAISEPLDKAPHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAIS FNFFQSYNQYYVFHMPRCLFAGPLAEQFLNQVDLTETLERYQQRLNTYQLVSKDLASYRSPSQQLKAQDSLGEQPTT VPPPIDLSIPHVWMPPQTTPHGWTESHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLLDELRYVKITLTE DFFVVTVSIDDDTPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLD LSALLRNSFHRYAVDVLKSGRCQMLDRPTVEMAFAYALALFAAAPQEEAGAQVSVPRALDPQAALLQIQEFMITCLS QTPPRTTLLLYPTAVDLAKPALWTPNQITDITSLVPLVYILSKQNQQHLIPQWALRQLADFALKLWKTHLASFLSAF ARQELYLMGSLVHSMLVHTTERREIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDHSLERLTRLF PDATVPTTVPAALSILSTMQPSTLETFPDLFCLPLGESFSALTVSEHVSYVVTNQYLIKGISYPVSTTVVGQSLIIT QTDSQTKCELTRNMHTTHSITAALNISLENCAFCQSALLEYDDTQGVININYMHDSDDVLFALDPYNEVVVSSPRTH YLMLLKNGTVLEVTDVVVDATDSRLLMMSVYALSAIIGIYLLYRMLKTC (gH from HCMV strain AD169 = GI:138313) SEQ ID NO: 3 MRPGLPPYLTVFRVYLLSHLPSQRYGADAASEALDPHAFHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAI SFNFFQSYNQYYVFHMPRCLFAGPLAEQFLNQVDLTETLERYQQPLNTYALVSKDLASYRSFSQQLKAQDSLGQQPT TVPPPIDLSIPHVWMPPQTTPHDWKGSHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLMDELPYVKITLT EDFFVVTVSIDDDTPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKAQLNRHSYLKDSDFLDAALDFNYL DLSALLRNSFHRYAVDVLKSGRCQMLDRRTVEMAFAYALALFAAARQEEAGTEISIPRALDRQAALLQIQEFMITCL SQTPPRTTLLLYPTAVDLAKRALWTPDQITDITSLVRLVYILSKQNQQHLIPQWALRQIADFALQLHKTHLASFLSA FPDATVPATVPAALSILSTMQPSTLETFPDLFCLPLGESFSALTVSEHVSYVVTNQYLIKGISYPVSTTVVGQSLII TQTDSQTKCELTPNMKTTHSITAALNISLENCAFCQSALLEYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRT HYLMLLKNGTVLEVTLVVVDATDSRLLMMSVYALSAIIGIYLLYRMLKTC (gH protein consisting of amino acid residues 1-715 of SEQ ID NO: 1) SEQ ID NO: 4 MRPGLPSYLIILAVCLFSHLLSSRYGAEAVSEPLDKAFHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAIS FNFFQSYNQYYVFHMPRCLFAGPLAEQFLNQVDLTETLERYQQPLNTYALVSKDLASYPSFSQQLKAQDSLGEQPTT VPPPIDLSIPHVWMPPQTTPHGHTESHTTSGLHPPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTE DFFVVTVSIDDDTPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLD LSALLRNSFGRYAVDVLKSGRCQMLDRRTVEMAFAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITLCS QTPPRTTLLLYPTAVDLAKRALWTPNQITDITSLVRLVYLLSKQNQQHLIPQWALPQIADFALKLMKTHLASFLSAF ARQLYLLMGSLVHSMLVHTTERREIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDHSLERLTRLF PDATVPATVPAALSILSTMQPSTLETFPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVSTTVVGQSLIIT QTDSQTKCELTPNMHTTHSITVALNISLENCAFCQSALLEYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTH YLMLLKNGTVLEVTDVVVDATD (C-terminal extension which includes a myc-tag and a polyhistidine-tag) SEQ ID NO: 5 GTKLGPEQKLISEEDLNSAVDHHHHHH (gH protein comprising SEQ ID NOs: 4 and 5) SEQ ID NO: 6 MRPGLPSYLIILAVCLFSHLLSSRYGAEAVSEPLDKAFHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAIS FNFFQSYNQYYVFHMPRCLFAGPLAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQLKAQDSLGEQPTT VPPPIDLSIPHVWMPPQTTPHGWTESHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELPYVKITLTE DFFVVTVSIDDDTPMLLIFGHLPRVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLD LSALLRNSFHRYAVDVLKSGRCQMLDRRTVEMAFAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITCLS QTPPRTTLLLYPTAVDLAKRALWTPNQITDITSLVRLVYILSKQNQQHLIPQWALRQIADFALKLHKTHLASFLSAF ARQELYLMGSLVHSMLVHTTERREIFIVETGLCSLAELSHFTQLLAHPRREYLSDLYRPCSSSGRRDHSLERLTRLF PDATVPATVPAALSILSTMQPSTLETPPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVSFFVVGQSLIIT QTDSQTKCELTRNMHTTHSITVALNISLENCAFCQSALLEYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTH YLMLLKNGTVLEVTDVVVDATDGTKLGPEQKLISEEDLNSAVDHHHHHH (gL from HCMV strain Merlin = GI:39842115) SEQ ID NO: 7 MCRRPDCGFSFSPGPVILLWCCLLLPIVSSAAVSVAPTAAEKVPAECPELTRRCLLGEVFEGDKYESWLRPLVNVTG RDGPLSQLIRYRPVTPEAANSVLLDEAFLDTLALLYNNPDQLRALLTLLSSDTAPRWMTVMRGYSECGDGSPAVYTC VDDLCRGYDLTRLSYGRSIFTEHVLGFELVPPSLENVVVALRNEATRTNRAVRLPVSTAAAPEGITLFYGLYNAVKE FCLRHQLDPPLLRHLDKYYAGLPPELKQTRVNLPAHSRYGPQAVDAR (gL from HCMV strain Towne = GI:239909463) SEQ ID NO: 8 MCRRPDCGFSFSPGPVALLWCCLLLPIVSSATVSVAPTVAEKVPAECPELTRRCLLGEVFQGDKYESWLRPLVNVTR RDGPLSQLIRYRPVTPEAAHSVLLDDAFLDTLALLYNNPDQLRALLTLLSSDTAPRWMTVMRGYSECGDGSPAVYTC VDDLCRGYDLTRLSYGRSIFTEHVLGFELVPPSLFNVVVAIRNEATRTNRAVRLPVSTAAAPEGITLFYGLYNAVKE FCLRHQLDPPLLRHLDKYYAGLPPELKQTRVNLPAHSPYGPQAVDAR (gL from HCMV strain AD169 = GI:2506510) SEQ ID NO: 9 MCRRPDCGFSFSPGPVVLLWCCLLLPIVSSVAVSVAPTAAEKVPAECPELTRRCLLGEVFQGDKYESWLRPLVNVTR RDGPLSQLIRYRPVTPEAANSVLLDDAFLDTLALLYNKPDQLRALLTLLSSDTAPRWMTVMRGYSECGDGSPAVYTC VDDLCRGYGLTRLSYGRSIFTEHVLGFELVPPSLFNVVVATRNEATRTNRAVRLPVSTAAAPEGITLFYGLYNAVKE FCLRHQLDPPLLRHLDKYYAGLPPELKQTRVNLPAHSRYGPQAVDAR (gO from HCMV strain Merlin = GI:39842082) SEQ ID NO: 10 MGKKEMIMVKGIPKIMLLISITFLLLSLINCNVLVNSFGTRRSWPYTVLSYRGKEILKKQKEDILKRLMSTSSDGYR FLMYPSQQKFHAIVISMDKFPQDYILAGPIRNDSITHMWFDFYSTQLRKPAKYVYSEYNKTAHKITLRPPPCGTVPS MNCLSEMLNVSKRNDTGEKGCGNFTTFNPMFFNVPRWKTKLYIGSNKVNVDSQTIYFLGLTALLLRYAQRNCTRSFY LVNAMSRNLFRVPKYINGTKLKNTMRKLKPKQALVKEQPQKKNKKSQSTTTPYLSYTTSTAFNVTTNVTYSATAAVT RVATSTTGYRPDSNFMKSIMATQKRDKATWVYTTLRYRNEPFCKPDRNRTAVSEFMKNTHVLIRNETPYTIYGTLDM SSLYYNETMSVENETASDNNETTPTSPSTRFQRTFIDPLWDYLDSLLFLDKIRNFSLQLPAYGNLTPPEHRRAANLS TLNSLWWWSQ (gO from HCMV strain AD169 = GI:136968) SEQ ID NO: 11 MGRKEMMVPDVPKMVFLISISFLLVSFINCKVMSKALYNRPWRGLVLSKIGKYKLDQLKLEILRQLETTISTKYNVS KQPVKNLTMNMTEFPQYYILAGPIQNYSITYLWFDFYSTQLRKPAKYVYSQYNHTAKTITFRPPPCGRVPSMTCLSE MLNVSKRNDTGEQGCGNFTTFNPMFFNVPRWNTKLYVGPTKVNVDSQTIYFLGLTALLLRYAQRNCTHSFYLVNAMS RNLFRVPKYINGTKLKNTMRKLKRKQAPVKEQFEKKAKKTQSTTTPYFSYTTSAALNVTTNVTYSITTAARRVSTST IAYRPDSSFMKSIMATQLRDLATWVYTTLRYRQNPFCEPSRNRTAVSEFMKNTHVLIRNETPYTIYGTLDMSSLYYN ETMFVENKTASDSNKTTPTSPSMGFQRTFIDPLWDYLDSLLFLDEIRNFSLRSPTYVNLTPPEHRRAVNLSTLNSLW WWLQ (gO from HCMV strain Towne = GI:239909431) SEQ ID NO: 12 MGRKGEMRGVFNLFFLMSLTFLLFSFINCKIAVARFRVKSQKAKEEERQLKLRILQELASKTGDYYKFFTFPSQQKL YNITVEMKQFPPNSILAGPIRNHSITHLWFDFHTTQLRKPAKYVYSEYNHTGQKITFRPPSCGTIPSMTCLSEMLNV SRRNNTGEENCGNFTTFNPMFFNVPRWNTKLYVGPSKVNVDSQTIYFLGLAALLLRYAQRNCTRSFYLVNAMSRNIF RVPKYINSTKLKNTMRKLKRKQAPVKSISKKSRVSTTTPYSSYTSTIFNVSTNVTYSPIVPTRIPTSTIGYRPDENF MKSILTTQLKDLATWVYTTLRYPDEPPCKPNRNRTAVSEFMKNTHVLIRNETPYTIYGTLDMSSLYYNDTMPVENET ASDNNKTTPTSPSTRFQRTFIDPMWDYLDSLLFLSEIRNFSLQSSTYGNLTPPEHRRAVNLSTLNSLWWWLQ (pUL128 from HCMV strain Merlin = GI:39942124) SEQ ID NO: 13 MSPKDLTPFLTALWLLLGHSRVPRVRAEECCEFLNVNEPPERCYDFKMCNPFTVALRCPDGEVCYSPEKTAEIRGIV TTMTHSLTRQVVHNKLTSCNYNPLYLEADGRIRCGKVNDKAQYLLGAAGSVPY (pUL128 from HCMV strain Towne = GI:39841882) SEQ ID NO: 14 MSPKDLTPFLTALWLLLGHSRVPRVRAEECCEFLNVNEPPERCYDFKMCNPFTVALRCPDGEVCYSPEKTAEIRGIV TTMTHSLTPQVVHNKLTSCNYNPLYLEADGRIRCGKVNDKAQYLLGAAGEVPYRWINLEYDKITRIVGLDQYLESVK KHKRLDVCRAKMGYMLQ (pUL128 from HCMV strain AD169 = GI:59803078) SEQ ID NO: 15 MSPKDLTPFLTTLWLLLGHSRVPRVRAEECCEFINVNEPPERCYDFKMCNRFTVALRCPDGEVCYSPEKTAEIRGIV TTMTHSLTRQVVHNKLTSCNYNPLYLEADGRIRCGKVNDKAQYLLGAAGSVPYRWINLEYDKITRIVGLDQYLESVK KHKRLDVCRAKMGYMLQ (pUL128 from HCMV strain Merlin = GI:39842125) SEQ ID NO: 16 MLRLLLRHHFHCLLLCAVWATPCLASPWSTLTANQNPSPPWSKLTYSKPHDAATFYCPFLYPSPPPSPLQFSGFQRV STGPECRNETLYLLYNREGQTLVPRSSTWVKKVIWYLSGRNQTILQRMPRTASKPSDGNVQISVELAKIFGAHMVPK QTKLLRFVVNDGTRYQMCVMKLESWAHVFRDYSVSFQVRLTFTEANNQTYTFCTHPNLIV (pUL130 from HCMV strain Towne = GI:239909473) SEQ ID NO: 17 MLRLLLRHHFHCLLLCAVWATPCLASPWSTLTANQNPSPPWSKLTYSKPHDAATFYCPFLYPSPPRSPLQFSGFQRV LTGPECRNETLYLLYNREGQRLVEPSSTWVKKVIWYLSGRNQTILQRMPRTASKPSDGNVQISVEDAKIFGAHMVPK QTKLLRFVVNDGTRYQMCVMKLESWAHVFRDYSVSFQVRLTFTEANNQTFTPSAPIPISSFEPVARAGNFENRAS (pUL131A from HCMV strain Merlin = GI:39842126) SEQ ID NO. 18 MRLCRVWLSVCLCAVVLGQCQRETAEKNDYYRVPHYWDACSRALPDQTRYKYVEQLVDLTLNYHYDASHGLDNFDVL KRINVTEVSLLISDFRRQNRRGGTNKRTTFNAAGSLAPHARSLEFSVRLFAN (pU1131A from HCMV strain Towne = GI:239209474) SEQ ID NO: 19 MRLCRVWLSVCLCAVVLGQCQRETAEKNDYYRVPHYWDACSRALPDQTRYKYVEQLVDLTLNYHYDASHGLDNFDVL KRINVTEVSLLISDFRRQNRRGGTNKRTTFNAAGSLAPHARSLEFSVRLFAN (pUL131A from HCMV strain AD169 = GI:219879712) SEQ ID NO: 20 MPLCRVWLSVCLCAVVLGQCQRETAEKKRLLPSTALLGRVLSRAARPNPLQVCGRARGPHVELPLRCEPRLGQL (gB from HCMV strain Merlin = GI:39842076) SEQ ID NO: 21 MESRIWCLVVCVBLCTVCLGAAVSSSSTRGTSATHSHESSHTTSAAHSRSGSVSQRVTSSQTVSHGVBETIYNTTLK YGDVVGVNTTKYPYRVCSMAQGTDLIRFERNIVCTSMKPINEDLDEGIMVVYKRNIVAHTFKVRVYQKVLTFRRSYA YIHTTYLLGSNTEYVAPPMWELHHINSHSQCYSSYSRVLAGTVFVAYHRDSYENKTMQLMPDDYSNTHSTPYVTVKD QWHSRGSTWLYRETCNLNCMVTITTARSKYPYHFFATSTGDVVDISPFYNGTNRNASYFGENADKFFIFFNYTIVSD FGPPNSALETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASERTIRSEAEDSYRFSSAKMTATFLSKKQEVNMS DSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVFETTGGLVVFWQGIKQKSLVELEPLANRSSLNLTHNRTKPST DGNNATHLSNMESVHNLVYAQLQFTYDTLRGYINRALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAA RFMGDVLGLASCVTINQTSVKVLRDMNVKESPGRCYSRPVVIFNFANSSYVQYGQLGEDNEILLGNHRTEECQLPSL KIFIAGNSAYEYVDYLFKRMIDLSSISTVDSMIALDIDPLENTDFRVLELYSQKELRSSNVFDLEEIMREFNSYKQR VKYVEDKVVDPLPPYLKGLDDLMSGLGAAGKAVGVAIGAVGGAVASVVEGVATFLKNPFGAGTIILVAIAVVIITYL IYTRQRRLCTQPLQNLFPYLVSADGTTVTSGSTKDTSLQAPPSYEESVYNSGRKGPGPPSSDASTAAPPYTNEQAYQ MLLALARLDAEQRAQQNGTDSLDGRTGTQDKGQKPNLLDRLRHRKNGYRHLKDSDEEENV (gB from RCMV strain Towne = GI:138193) SEQ ID NO: 22 MESRIWCLVVCVNLCIVCLGAAVSSSSTRGTSATHSHHSSHTTSAAHSRSGSVSQRVTSSQTVSHGVNETIYNTTLK YGDVVGVNTTKYPYRVCSMAQGTDLIRFERNIVCTSMKPINEDLDEGIMVVYKPNIVAHTFKVRVYQKVLTFRRSYA YIHTTYLLGSNTEYVAPPMWEIHHINSHSQCYSSYSRVIAGTVFVAYHRDSYENKTMQLMPDDYSNTHSTRYVTVKD QWHSRGSTWLYRETCNLNCMVTITTARSKYPYHFFATSTGDVVDISPFYNGTNRNASYFGENADKFFIPPNYTIVSD FGRPNSALETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASERTIRSEAEDSYHFSSAKMTATFLSKKQEVNMS DSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVPETTGGLVVFWQFIKQKSLVELERLANRSSLNLTHNRTKRST DGNNATHLSNMESVHNLVYAQLQFRYDTLRGYINRALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAA RFMGDVLGLASCVTINQTSVKVLRDMNVKESPGRCYSRPVVIFNFANSSYVQYGQLGEDNEILLGNHRTEECQLPSL KIFLAGNSAYEYVDYLFKRMLDLSSISTVDSMIALDIDPLENTDFRVLELYSQKEPRSSNVFDLEEIMREFNSYKQR VKYVEDKVVDPLPPYLKGLDDLMSGLGAAGLAVGVAIGAVGGAVASVVEGVATFLKNPFGAFTIILVAIAVVIIIYL IYTRQRRLCMQPLQNLFPYLVSADGTTVTSGNTKDTSLQAPPSYEESVYNSGRKGPGPPSSDASTAAPPYTNEQAYQ MLLALVRLDAEQRAQQNGTDSLDGQTGTQDKGQKPNLLDRLRHPKNGYRNLKDSDEEENV (gB from HCMV strain AD169 = GI:138192) SEQ ID NO: 23 MESRIWCLVVCVNLCIVCLGAAVSSSSTSHATSSTHNGSHTSRTTSAQTRSVYSQHVTSSEAVSHRANETIYNTTLK YGDVVGVNTTKYPYRVCSMAQGTDLIRFERNIICTSMKPINEDLDEGIMVVYKRNIVAHTFKVRVYQKVLTFRRSYA YIYTTYLLGSNTEYVAPPMWEIHHINKFAQCYSSYSRVIGGTVFVAYHRDSYENKTMQLIPDDYSNTHSTRYVTVKD QWHSRGSTWLYRETCNLNCMLTITTARSKYPYHFFATSTGDVVYISPFYNGTNPNASYFGENADKFFIFPNYTIVSD FGRPNAAPETHRLVAFLERADSVISWDIQDEKNVTCQLTFWEASEPTIRSEAEDSYHFSSAKMTATFLSKKQEVNMS DSALDCVRDEAINKLQQIFNTSYNQTYEKYGNVSVFETSGGLVVFWQFIKQKSLVELERLANRSSLNITHRTRRSTS DNNTTHLSSMESVHNLVYAQLQFTYDTLRGYINRALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAAR FMGDVLGLASCVTINQTSVKVLRDMNVKESPGRCYSRPVVIFNFANSSYVQYGQLGEDNEILLGNHRTEECQLPSLK IFIAGNSAYEYVDYLFKRMIDLSSISTVDSMIALDIDPLENTDFPVLELYSQKELRSSNVFDLEEIMREFNSYKQRV KYVEDKVVDPLPPYLKGLDDLMSGLGAAGKAVGVAIGAVGGAVASVVEGVATFLKNPFGAFTIILVALAVVIITYLI YTRQRRLCTQPLQNLFPYLVSADGTTVTSGSTKDTSLQAPPSYEESVYNSGRKGPGPPSSDASTAAPPYTNEQAYQM LLALLRLDAEQRAQQNGTDSLDGQTGTQDKGQKPNLLDRLRHRKNGYRHLKDSDEEENV (a construct encoding gH(ecto) fused to a C-terminal myc-(His)6 tag) SEQ ID NO: 24 gacggatcgggagatctcccgatcccctatggtgcactctcagtacaatctgctctgatgccgcatagttaagccag tatctgctccctgcttgtgtgttggaggtcgctgagtagtgcgcgagcaaaatttaagctacaacaaggcaaggctt gaccgacaattgcatgaagaatctgcttagggttaggcgttttgcgctgcttcgcgatgtacgggccagatatacgc gttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagcccatatatggagttc cgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccattgacgtcaataatgac gtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttacggtaaactgcccact tggcagtacatcaagtgtatcatatgccaagtacgccccctattgacgtcaatgacggtaaatggcccgcctggcat tatgcccagtacatgaccttatgggactttcctacttggcagtacatctacgtattagtcatcgctattaccatggt gatgcggttttggcagtacatcaatgggcgtggatagcggtttgactcacggggatttccaagtctccaccccattg acgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaacaactccgccccattgacg caaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctctctggctaactagagaacccactgctta ctggcttatcgaaattaatacgactcactatagggagacccaagctggctagcgccaccatgaggcctggcctgccc tcctacctgatcatcctggccgtgtgcctgttcagccacctgctgtccagcagatacggcgccgaggccgtgagcga gcccctggacaaggctttccacctgctgctgaacacctacggcagacccatccggtttctgcgggagaacaccaccc agtgcacctacaacagcagcctgcggaacagcaccgtcgtgagagagaacgccatcagcttcaactttttccagagc tacaaccagtactacgtgttccacatgcccagatgcctgtttgccggccctctggccgagcagttcctgaaccaggt ggacctgaccgagacactggaaagataccagcagcggctgaatacctacgccctggtgtccaaggacctggccagct accggtcctttagccagcagctcaaggctcaggatagcctcggcgagcagcctaccaccgtgccccctcccatcgac ctgagcatcccccacgtgtggatgcctccccagaccacccctcacggctggaccgagagccacaccacctccggcct gcacagaccccacttcaaccagacctgcatcctgttcgacggccacgacctgctgtttagcaccgtgaccccctgcc tgcaccagggcttctacctgatcgacgagctgagatacgtgaagatcaccctgaccgaggatttcttcgtggtcacc gtgtccatcgacgacgacacccccatgctgctgatcttcggccacctgcccagagtgctgttcaaggccccctacca gcgggacaacttcatcctgcggcagaccgagaagcacgagctgctggtgctggtcaagaaggaccagctgaaccggc actcctacctgaaggaccccgacttcctggacgccgccctggacttcaactacctggacctgagcgccctgctgaga aacagcttccacagatacgccgtggacgtgctgaagtccggacggtgccagatgctcgatcggcggaccgtggagat ggccttcgcctatgccctcgccctgttcgccgctgccagacaggaagaggctggcgcccaggtgtcagtgcccagag ccctggatagacaggccgccctgctgcagatccaggaattcatgatcacctgcctgagccagaccccccctagaacc accctgctgctgtaccccacagccgtggatctggccaagagggccctgtggacccccaaccagatcaccgacatcac aagcctcgtgcggctcgtgtacatcctgagcaagcagaaccagcagcacctgatcccccagtgggccctgagacaga tcgccgacttcgccctgaagctgcacaagacccatctggccagctttctgagcgccttcgccaggcaggaactgtac ctgatgggcagcctggtccacagcatgctggtgcataccaccgagcggcgggagatcttcatcgtggagacaggcct gtgtagcctggccgagctgtcccactttacccagctgctggcccaccctcaccacgagtacctgagcgacctgtaca ccccctgcagcagcagcggcagacgggaccacagcctggaacggctgaccagactgttccccgatgccaccgtgcct gctacagtgcctgccgccctgtccatcctgtccaccatgcagcccagcaccctggaaaccttccccgacctgttctg cctgcccctgggcgagagctttagcgccctgaccgtgtccgagcacgtgtcctacatcgtgaccaatcagtacctga tcaagggcatcagctaccccgtgtccaccacagtcgtgggccagagcctgatcatcacccagaccgacagccagacc aagtgcagactgacccggaacatgcacaccacacacagcatcaccgtggccctgaacatcagcctggaaaactgcgc tttctgtcagtctgccctgctggaatacgacgatacccagggcgtgatcaacatcatgtacatgcacgacagcgacg acgtgctgttcgccctggacccctacaacgaggtggtggtgtccagcccccggacccactacctgatgctgctgaag aacggcaccgtgctggaagtgaccgacgtggtggtggacgccaccgacggtaccaagcttgggcccgaacaaaaact catctcagaagaggatctgaatagcgccgtcgaccatcatcatcatcatcattgagtttaaacggtctccagcttaa gtttaaaccgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttcc ttgaccctggaaggtgccactcccactgrcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtg tcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggcatgctgggg atgcggtgggctctatggcttctgaggcggaaagaaccagctggggctctagggggtatccccacgcgccctgtagc ggcgcattaagcgcggcgggtgtggtggttacgcgcagcgtgaccgctacacttgccagcgccctagcgcccgctcc tttcgctttcttcccttcctttctcgccacgttcgccggctttccccgtcaagctctaaatcgggggctccctttag ggttccgatttagtgctttacggcacctcgaccccaaaaaacttgattagggtgatggttcacgtagtgggccatcg ccctgatagacggtttttcgccctttgacgttggagtccacgttctttaatagtggactcttgttccaaactggaac aacactcaaccctatctcggtctattcttttgatttataagggattttgccgatttcggcctattggttaaaaaatg agctgatttaacaaaaatttaacgcgaattaattctgtggaatgtgtgtcagttagggtgtggaaagtccccaggct ccccagcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccaggtgtggaaagtccccaggctcccca gcaggcagaagtatgcaaagcatgcatctcaattagtcagcaaccatagtcccgcccctaactccgcccatcccgcc cctaactccgcccagttccgcccattctccgccccatggctgactaattttttttatttatgcagaggccgaggccg cctctgcctctgagctattccagaagtagtgaggaggcttttttggaggcctaggcttttgcaaaaagctcccggga gcttgtatatccattttcggatctgatcaagagacaggatgaggatcgtttcgcatgattgaacaagatggattgca cgcaggttctccggccgcttgggtggagaggctattcggctatgactgggcacaacagacaatcggctgctctgatg ccgccgtgttccggctgtcagcgcaggggcgcccggttctttttgtcaagaccgacctgtccggtgccctgaatgaa ctgcaggacgaggcagcgcggctatcgtggctggccacgacgggcgttccttgcgcagctgtgctcgacgttgtcac tgaagcgggaagggactggctgctattgggcgaagtgccggggcaggatctcctgtcatctcaccttgctcctgccg agaaagtatccatcatggctgatgcaatgcggcggctgcatacgcttgatccggctacctgcccattcgaccaccaa gcgaaacatcgcatcgagcgagcacgtactcggatggaagccggtcttgtcgatcaggatgatctggacgaagagca tcaggggctcgcgccagccgaactgttcgccaggctcaaggcgcgcatgcccgacggcgaggatctcgtcgtgaccc atggcgatgcctgcttgccgaatatcatggtggaaaatggccgcttttctggattcatcgactgtggccggctgggt gtggcggaccgctatcaggacatagcgttggctacccgtgatattgctgaagagcttggcggcgaatgggctgaccg cttcctcgtgctttacggtatcgccgctcccgattcgcagcgcatcgccttctatcgccttcttgacgagttcttct gagcgggactctggggttcgaaatgaccgaccaagcgacgcccaacctfccatcacgagatttcgattccaccgccg ccttctatgaaaggttgggcttcggaatcgttttccgggacgccggctggatgatcctccagcgcggggatctcatg ctggagttcttcgcccaccccaacttgtttattgcagcttataatggttacaaataaagcaatagcatcacaaattt cacaaataaagcatttttttcactgcattctagttgtggtttgtccaaactcatcaatgtatcttatcatgtctgta taccgtcgacctctagctagagcttggcgtaatcatggtcatagctgtttcctgtgtgaaattgttatccgctcaca attccacacaacatacgagccggaagcataaagtgtaaagcctggggtgcctaatgagtgagctaactcacattaat tgcgttgcgctcactgcccgctttccagtcgggaaacctgtcgtgccagctgcattaatgaatcggccaacgcgcgg ggagaggcggtttgcgtattgggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcgg cgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtg agcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctg acgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccc cctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcggg aagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtg tgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacac gacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttctt gaagtggtggcctaactacggctacactagaagaacagtatttggtatctgvgctctgctgaagccagttaccttcg gaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcag attacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctacggggtctgacgctcagtggaacgaaaa ctcacgttaagggattttggtcatgagattatcaaaaaggatcttcacctagatccttttaaattaaaaatgaagtt ttaaatcaatctaaagtatatatgagtaaacttggtctgacagttaccaatgcttaatcagtgaggcacctatctca gcgatctgtctatttcgttcatccatagttgcctgactccccgtcgtgtagataactacgatacgggagggcttacc atctggccccagtgctgcaatgataccgcgagacccacgctcaccggctccagatttatcagcaataaaccagccag ccggaagggccgagcgcagaagtggtcctgcaactttatccgcctccatccagtctattaattgttgccgggaagct agagtaagtagttcgccagttaatagtttgcgcaacgttgttgccattgctacaggcatcgtggtgtcacgctcgtc gtttggtatggcttcattcagctccggttcccaacgatcaaggcgagttacatgatcccccatgttgtgcaaaaaag cggttagctccttcggtcctccgatcgttgtcagaagtaagttggccgcagtgttatcactcatggttatggcagca ctgcataattctcttactgtcatgccatccgtaagatgcttttctgtgactggtgagtactcaaccaagtcattctg agaatagtgtatgcggcgaccgagttgctcttgcccggcgtgaatacgggataataccgcgccacatagcagaactt taaaagtgctcatcattggaaaacgttcttcggggcgaaaactctcaaggatcttaccgctgttgagatccagttcg atgtaacccactcgtgcacccaactgatcttcagcatcttttactttcaccagcgtttctgggtgagcaaaaacagg aaggcaaaatgccgcaaaaaagggaataagggcgacacggaaatgttgaatactcatactcttcctttttcaatatt attgaagcatttatcagggttattgtctcatgagcggatacatatttgaatgtatttagaaaaataaacaaataggg gttccgcgcacatttccccgaaaagtgccacctgacgtc (a construct encoding full-length gL) SEQ ID NO: 25 gccgcggaatttcgactctaggccattgcatacgttgtatctatatcataatatgtacatttatattggctcatgtc caatatgaccgccatgttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagc ccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccatt gacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttac ggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtccgccccctattgacgtcaatgacggtaaa tggcccgcctggcattatgcccagtacatgaccttacgggactttcctacttggcagtacatctacgtattagtcat cgctattaccatggtgatgcggttttggcagtacaccaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaataac cccgccccgttgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtttagtgaaccg tcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagcctccgcggcc gggaacggtgcattggaacgcggattccccgtgccaagagtgacgtaagtaccgcctatagactctataggcacacc cctttggctcttatgcatgctatactgtttttggcttggggcctatacacccccgcttccttatgctataggtgatg gtatagcttagcctataggtgtgggttattgaccattattgaccactcccctattggtgacgatactttccattact aatccataacatggctctttgccacaactatctctattggctatatgccaatactctgtccttcagagactgacacg gactctgtatttttacaggatggggtcccatttattatttacaaattcacatatacaacaacgccgtcccccgtgcc cgcagtttttattaaacatagcgtgggatctccacgcgaatctcgggtacgtgttccggacatgggctcttctccgg tagcggcggagcttccacatccgagccctggtcccatgcctccagcggctcatggtcgctcggcagctccttgctcc taacagyggaggccagacttaggcacagcacaatgcccaccaccaccagtgtgccgcacaaggccgtggcggtaggg tatgtgtctgaaaatgagctcggagattgggctcgcaccgctgacgcagatggaagacttaaggcagcggcagaaga agatgcaggcagctgagttgttgtattctgataagagtcagaggtaactcccgttgcggtgctgttaacggtggagg gcagtgtagtctgagcagtactcgttgctgccgcgcgcgccaccagacataatagctgacagactaacagactgttc ctttccatgggtcttttctgcagtcaccgtcgtcgacgccaccatgtgcagaaggcccgactgcggcttcagcttca gccctggacccgtgatcctgctgtggtgctgcctgctgctgcctatcgtgtcctctgccgccgtgtctgtggcccct acagccgccgagaaggtgccagccgagtgccccgagctgaccagaagatgcctgctgggcgaggtgttcgagggcga caagtacgagagctggctgcggcccctggtcaacgtgaccggcagagatggccccctgagccagctgatccggtaca gacccgtgacccccgaggccgccaatagcgtgctgctggacgaggccttcctggataccctggccctgctgtacaac aaccccgaccagctgagagccctgctgaccctgctgtccagcgacaccgcccccagatggatgaccgtgatgcgggg ctacagcgagtgtggagatggcagccctgccgtgtacacctgcgtggacgacctgtgcagaggctacgacctgacca gactgagctacggccggtccatcttcacagagcacgtgctgggcttcgagctggtgccccccagcctgttcaacgtg gtggtggccatccggaacgaggccaccagaaccaagagagccgtgcggctgcctgtgtctacagccgctgcacctga gggcatcacactgttctacggcctgtacaacgccgtgaaagagttctgcctccggcaccagctggatccccccctgc tgagacacctggacaagtactacgccggcctgcccccagagctgaagcagaccagagtgaacctgcccgcccacagc agatatggccctcaggccgtggacgccagatgataatctagaaagccatggatatcggatccactacgcgttagagc tcgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccc tggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattct attctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcaggggggtgggcgaagaact ccagcatgagatccccgcgctggaggatcatccagccggcgtcccggaaaacgattccgaagcccaacctttcatag aaggcggcggtggaatcgaaatctcgtgatggcaggttgggcgtcgcttggtcggtcatttcgaaccccagagtccc gctcagaagaactcgtcaagaaggcgatagaaggcgatgcgctgcgaatcgggagaggcgataccgtaaagcacgag gaagcggtcagcccattcgccgccaagctcttcagcaatatcacgggtagccaacgctatgtcctgatagcggtccg ccacacccagccggccacagtcgatgaatccagaaaagcggccattttccaccatgatattcggcaagcaggcatcg ccatgggtcacgacgagatcctcgccgtcgggcatgcgcgccttgagcctggcgaacagttcggctggcgcgagccc ctgatgctcttcgtccagatcatcctgatcgacaagaccggcttccatccgagtacgtgctcgctcgatgcgatgtt tcgcttggtggtcgaatgggcaggtagccggatcaagcgtatgcagccgccgcattgcatcagccatgatggatact ttctcggcaggagcaaggtgagatgacaggagatcctgccccggcacttcgcccaatagcagccagtcccttcccgc ttcagtgacaacgtcgagcacagctgcgcaaggaacgcccgtcgtggccagccacgatagccgcgctgcctcgtcct gcagttcattcagggcaccggacaggtcggtcttgacaaaaagaaccgggcgcccctgcgctgacagccggaacacg gcggcatcagagcagccgattgtctgttgtgcccagtcatagccgaatagcctctccacccaagcggccggagaacc tgcgtgcaatccatcttgttcaatcatgcgaaacgatcctcatcctgtctcttgatcagatcttgatcccctgcgcc atcagatccttggcggcaagaaagccatccagtttactttgcagggcttcccaaccttaccagagggcgccccagct ggcaattccggttcgcttgctgtccataaaaccgcccagtctagctatcgccatgtaagcccactgcaagctacctg ctttctctttgcgcttgcgttttcccttgtccagatagcccagtagctgacattcatccggggtcagcaccgtttct gcggactggctttctacgtgttccgcttcctttagcagcccttgcgccctgagtgcttgcggcagcgtgaagctaat tcatggttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaa agaatagcccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacg tcaaagggcgaaaaaccgtctatcagggcgatggccggatcagcttatgcggtgtgaaataccgcacagatgcgtaa ggagaaaataccgcatcaggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcga gcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagc aaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacg agcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccct ggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaag cgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgc acgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgac ttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaa gtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaa aaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagatt acgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctactgaacggtgatccccaccggaattgcg (a construct encoding full-length pUL128) SEQ ID NO: 26 gccgcggaatttcgactctaggccattgcatacgttgtatctatatcataatatgtacatttatattggctcatgtc caatatgaccgccatcttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagc ccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccatt gacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttac ggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtccgccccctattgacgtcaatgacggtaaa tggcccgcctggcattatgcccagtacatgaccttacgggactttcctacttggcagtacatctacgtattagtcat cgctattaccatggtgatgcggttttggcagtacaccaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaataac cccgccccgttgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtttagtgaaccg tcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagcctccgcggcc gggaacggtgcattggaacgcggattccccgtgccaagagtgacgtaagtaccgcctatagactctataggcacacc cctttggctcttatgcatgctatactgtttttggcttggggcctatacacccccgcttccttatgctataggtgatg gtatagcttagcctataggtgtgggttattgaccattattgaccactcccctattggtgacgatactttccattact aatccataacatggctctttgccacaactatctctattggctatatgccaatactctgtccttcagagactgacacg gactctgtatttttacaggatggggtcccatttattatttacaaattcacatatacaacaacgccgtcccccgtgcc cgcagtttttattaaacatagcgtgggatctccacgcgaatctcgggtacgtgttccggacatgggctcttctccgg tagcggcggagcttccacatccgagccctggtcccatgcctccagcggctcatggtcgctcggcagctccttgctcc taacagtggaggccagacttaggcacagcacaatgcccaccaccaccagtgtgccgcacaaggccgtggcggtaggg tatgtgtctgaaaatgagctcggagattgggctcgcaccgctgacgcagatggaagacttaaggcagcggcagaaga agatgcaggcagctgagttgttgtattctgataagagtcagaggtaactcccgttgcggtgctgttaacggtggagg gcagtgtagtctgagcagtactcgttgctgccgcgcgcgccaccagacataatagctgacagactaacagactgttc ctttccatgggtcttttctgcagtcaccgtcgtcgacgccccatgaggccccaaggacctgacccccttcctgacaa ccctgtggctgctcctgggccatagcagagtgcctagagtgcgggccgaggaatgctgcgagttcatcaacgtgaac cacccccccgagcggtgctacgacttcaagatgtgcaaccggttcaccgtggccctgagatgccccgacggcgaagt gtgctacagccccgagaaaaccgccgagatccggggcatcgtgaccaccatgacccacagcctgacccggcaggtgg tgcacaacaagctgaccagctgcaactacaaccccctgtacctggaagccgacggccggatcagatgcggcaaagtg aacgacaaggcccagtacctgctgggagccgccggaagcgtgccctaccggtggatcaacctggaatacgacaagat cacccggatcgtgggcctggaccagtacctggaaagcgtgaagaagcacaagcggctggacgtgtgcagagccaaga tgggctacatgctgcagtgataatctagaaagccatggatatcggatccactacgcgttagagctcgctgatcagcc tcgactgtgccttctagttgccagccatctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccac tcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtg gggtggggcaggacagcaagggggaggattgggaagacaatagcaggggggtgggcgaagaactccagcatgagatc cccgcgctggaggatcatccagccggcgtcccggaaaacgattccgaagcccaacctttcatagaaggcggcggtgg aatcgaaatctcgtgatggcaggttgggcgtcgcttggtcggtcatttcgaaccccagagtcccgctcagaagaact cgtcaagaaggcgatagaaggcgatgcgctgcgaatcgggagcggcgataccgtaaagcacgaggaagcggtcagcc cattcgccgccaagctcttcagcaatatcacgggtagccaacgctatgtcctgatagcggtccgccacacccagccg gccacagtcgatgaatccagaaaagcggccattttccaccatgctattcggcaagcaggcatcgccatgggtcacga cgagatcctcgccgtcgggcatgcgcgccttgagcctggcgaacagttcggctggcgcgagcccctgatgctcttcg tccagatcatcctgatcgacaagaccggcttccatccgagtacgtgctcgctcgatgcgatgtttcgcttggtggtc gaatgggcaggtagccggatcaagcgtatgcagccgccgcattgcatcagccatgatggatactttctcggcaggag caaggtgagatgacaggagatcctgccccggcacttcgcccaatagcagccagtcccttcccgcttcagtgacaacg tcgagcacagctgcgcaaggaacgcccgtcgtggccagccacgatagccgcgctgcctcgtcctgcagttcattcag ggcaccggacaggtcggtcttgacaaaaagaaccgggcgcccctgcgctgacagccggaacacggcggcatcagagc agccgattgtctgttgtgcccagtcatagccgaatagcctgtccacccaagcggccggagaacctgcgtgcaatcca tcttgttcaatcatgcgaaacgatcctcatcctgtctcttgatcagatcttgatcccctgcgccatcagatccttgg cggcaagaaagccatccagtttactttgcagggcttcccaaccttaccagagggcgccccagctggcaattccggtt cgcttgctgtccataaaaccgcccagtctagctatcgccatgtaagcccactgcaagctacctgctttctctttgcg cttgcgttttcccttgtccagatagcccagtagctgacattcatccggggtcagcaccgtttctgcggactggcttt ctacgtgttccgcttcctttagcagcccttgcgccctgagtgcttgcggcagcgtgaagctaattcatggttaaatt tttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagcccgag atagggttgagtgttgttccagtttggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaa aaccgtctatcagggcgatggccggatcagcttatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccg catcaggcgctcttccgcttcctcgctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctc actcaaaggcggtaatacggttatccacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaa aaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaa tcgacgctcaagtcagaggtggcgaaacccgacaggactataaagataccaggcgtttccccctggaagctccctcg tgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttct catagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgt tcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactgg cagcagccagtggtaacaggattagcagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaac tacggctacactagaaggacagtatttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtag ctcttgatccggcaaagaaaccaccgctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaa aaggatctcaagaagatcctttgatcttttctactgaacggtgatccccaccggaattgcg (a construct encoding full-length pUL130) SEQ ID NO: 27 gccgcggaatttcgactctaggccattgcatacgttgtatctatatcataatatgtacatttatattggctcatgtc caatatgaccgccatgttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagc ccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccatt gacgtcaataatgacgtatgttcccatagtaacgccaatagggactttccattgacgtcaatgggtggagtatttac ggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtccgccccctattgacgtcaatgacggtaaa tggcccgcctggcattatgcccagtacatgaccttacgggactttcctacttggcagtacatctacgtattagtcat cgctattaccatggtgatgcggttttggcagtacaccaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaataac cccgccccgttgacgcaaaygggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtttagtgaaccg tcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagcctccgcggcc gggaacggtgcattggaacgcggattccccgtgccaagagtgacgtaagtaccgcctatagactctataggcacacc cctttggctcttatgcatgctatactgtttttggcttggggcctatacacccccgcttccttatgctataggtgatg gtatagcttagcctataggtgtgggttattgaccattattgaccactcccctattggtgacgatactttccattact aatccataacatggctctttgccacaactatctctattggctatatgccaatactctgtccttcagagactgacacg gactctgtatttttacaggatggggtcccatttattatttacaaattcacatatacaacaacgccgtcccccgtgcc cgcagtttttattaaacatagcgtgggatctccacgcgaatctcgggtacgtgttccggacatgggctcttctccgg tagcggcggagcttccacatccgagccctggtcccatgcctccagcggctcatggtcgctcggcagctccttgctcc taacagtggaggccagacttaggcacagcacaatgcccaccaccaccagtgtgccgcacaaggccgtggcggtaggg tatgtgtctgaaaatgagctcggagattgggctcgcaccgctgacgcagatggaagacttaaggcagcggcagaaga agatgcaggcagctgagttgttgtattctgataagagtcagaggtaactcccgttgcggtgctgttaacggtggagg gcagtgtagtctgagcagtactcgttcgtgccgcgcgcgccaccagacataatagctgacagactaacagactgttc ctttccatgggtcttttctgcagtcaccgtcgtcgaccccaccatgctgcggctgctgctgagacaccacttccact gcctgctgctgtgtgccgtgtgggccaccccttgtctggccagcccttggagcaccctgaccgccaaccagaaccct agccccccttggtccaagctgacctacagcaagccccacgacgccgccaccttctactgcccctttctgtaccccag ccctcccagaagccccctgcagttcagcggcttccagagagtgtccaccggccctgagtgccggaacgagacactgt acctgctgtacaaccgggagggccagacactggtggagcggagcagcacctgggtgaaaaaagtgatctggtatctg agcggccggaaccagaccatcctgcagcggatgcccagaaccgccagcaagcccagcgacggcaacgtgcagatcag cgtggaggacgccaaaatcttcggcgcccacatggtgcccaagcagaccaagctgctgagattcgtggtcaacgacg gcaccagatatcagatgtgcgtgatgaagctggaaagctgggcccacgtgttccgggactactccgtgagcttccag gtccggctgaccttcaccgaggccaacaaccagacctacaccttctgcacccaccccaacctgatcgtgtgataatc tagaaagccatggatatcggatccactacgcgttagagctcgctgatcagcctcgactgtgccttctagttgccagc catctgttgtttgcccctcccccgtgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaat gaggaaattgcatcgcattgtctgagtaggtgtcattctattctggggggtggggtggggcaggacagcaaggggga ggattgggaagacaatagcaggggggtgggcgaagaactccagcatgagatccccgcgctggaggatcatccagccg gcgtcccggaaaacgattccgaagcccaacctttcatagaaggcggcggtggaatcgaaatctcgtgatggcaggtt gggcgtcgcttggtcggtcatttcgaaccccagagtcccgctcagaagaactcgtcaagaaggcgatagaaggcgat gcgctgcgaatcgggagcggcgataccgtaaagcacgaggaagcggtcagcccattcgccgccaagctcttcagcaa tatcacgggtagccaacgctatgtcctgatagcggtccgccacacccagccggccacagtcgatgaatccagaaaag cggccattttccaccatgatattcggcaagcaggcatcgccatgggtcacgacgagatcctcgccgtcgggcatgcg cgccttgagcctggcgaacagttcggctggcgcgagcccctgatgctcttcgtccagatcatcctgatcgacaagac cggcttccatccgagtacgtgctcgctcgatgcgatgtttcgcttggtggtcgaatgggcaggtagccggatcaagc gtatgcagccgccgcattgcatcagccatgatggatactttctcggcaggagcaaggtgagatgacaggagatcctg ccccggcacttcgcccaatagcagccagtcccttcccgcttcagtgacaacgtcgagcacagctgcgcaaggaacgc ccgtcgtggccagccacgatagccgcgctgcctcgtcctgcagttcattcagggcaccggacaggtcggtcttgaca aaaagaaccgggcgcccctgcgctgacagccggaacacggcggcatcagagcagccgattgtctgttgtgcccagtc atagccgaatagcctctccacccaagcggccggagaacctgcgtgcaatccatcttgttcaatcatgcgaaacgatc ctcatcctgtctcttgatcagatcttgatcccctgcgccatcagatccttggcggcaagaaagccatccagtttact ttgcagggcttcccaaccttaccagagggcgccccagctggcaattccggttcgcttgctgtccataaaaccgccca gtctagctatcgccatgtaagcccactgcaagctacctgctttctctttgcgcttgcgttttcccttgtccagatag cccagtagctgacattcatccggggtcagcaccgtttctgcggactggctttctacgtgttccgcttcctttagcag cccttgcgccctgagtgcttgcggcagcgtgaagctaattcatggttaaatttttgttaaatcagctcattttttaa ccaataggccgaaatcggcaaaatcccttataaatcaaaagaatagcccgagatagggttgagtgttgttccagttt ggaacaagagtccactattaaagaacgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggccgg atcagcttatgcggtgtgaaataccgcacagatgcgtaaggagaaaataccgcatcaggcgctcttccgcttcctcg ctcactgactcgctgcgctcggtcgttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatc cacagaatcaggggataacgcaggaaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccg cgttgctggcgtttttccataggctccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcga aacccgacaggactataaagataccaggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgcc gcttaccggatacctgtccgcctttctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctca gttcggtgtaggtcgttcgctccaagctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatcc ggtaactatcgtcttgagtccaacccggtaagacacgacttatcgccactggcagcagccactggtaacaggattag cagagcgaggtatgtaggcggtgctacagagttcttgaagtggtggcctaactacggctacactagaaggacagtat ttggtatctgcgctctgctgaagccagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccacc gctggtagcggtggtttttttgtttgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgat cttttctactgaacggtgatccccaccggaattgcg (a construct encoding full-length pUL131A) SEQ ID NO: 28 gccgcggaatttcgactctaggccattgcatacgttgtatctatatcataatatgtacatttatattggctcatgtc caatatgaccgccatgttgacattgattattgactagttattaatagtaatcaattacggggtcattagttcatagc ccatatatggagttccgcgttacataacttacggtaaatggcccgcctggctgaccgcccaacgacccccgcccatt gacgtcaataatgacgtatgttcccatagtaacgaaggtagggactttccattgacgtcaatgggtggagtatttac ggtaaactgcccacttggcagtacatcaagtgtatcatatgccaagtccgccccctattgacgtcaatgacggtaaa tggcccgcctggcattatgcccagtacatgaccttacgggactttcctacttggcagtacatctacgtattagtcat cgctattaccatggtgatgcggttttggcagtacaccaatgggcgtggatagcggtttgactcacggggatttccaa gtctccaccccattgacgtcaatgggagtttgttttggcaccaaaatcaacgggactttccaaaatgtcgtaataac cccgccccgttgacgcaaatgggcggtaggcgtgtacggtgggaggtctatataagcagagctcgtttagtgaaccg tcagatcgcctggagacgccatccacgctgttttgacctccatagaagacaccgggaccgatccagcctccgcggcc gggaacggtgcattggaacgcggattccccgtgccaagagtgacgtaagtaccgcctatagactctataggcacacc cctttggctcttatgcatcgtatactgtttttggcttggggcctatacacccccgcttccttatgctataggtgatg gtatagcttagcctataggtgtgggttattgaccattattgaccactcccctattggtgacgatactttccattact aatccataacatggctctttgccacaactatctctattggctatatgccaatactctgtccttcagagactgacacg gactctgtatttttacaggatggggtcccatttattatttacaaattcacatatacaacaacgccgtcccccgtgcc cgcagtttttattaaacatagcgtgggatctccacgcgaatctcgggtacgtgttccggacatgggctcttctccgg tagcggcggagcttccacatccgagccctggtcccatgcctccagcggctcatggtcgctcggcagctccttgctcc taacagtggaggccagacttaggcacagcacaatgcccaccaccaccagtgtgccgcacaaggccgtggcggtaggg tatgtgtctgaaaatgagctcggagattgggctcgcaccgctgacgcagatggaagacttaaggcagcggcagaaga agatgcaggcagctgagttgttgtattctgataagagtcagaggtaactcccgttgcggtgctgttaacggtggagg gcagtgtagtctgagcagtactcgttgctgccgcgcgcgccaccagacataatagctgacagactaacagactgttc ctttccatgggtcttttctgcagtcaccgtcgtcgacgccaccatgcggctgtgcagagtgtggctgtccgtgtgcc tgtgtgccgtggtgctgggccagtgccagagagagacagccgagaagaacgactactaccgggtgccccactagtgg gatgcctgcagcagagccctgcccgaccagacccggtacaaatacgtggagcagctcgtggacctgaccctgaacta ccactacgacgccagccacggcctggacaacttcgacgtgctgaagcggatcaacgtgaccgacctgtccctgctga tcagcgacttccggcggcagaacagaagaggcggcaccaacaagcggaccaccttcaacgccgctggctctctggcc cctcacgccagatccctggaattcagcgtgcggctgttcgccaactgataatctagaaagccatggatatcggatcc actacgcgttagagctcgctgatcagcctcgactgtgccttctagttgccagccatctgttgtttgcccctcccccg tgccttccttgaccctggaaggtgccactcccactgtcctttcctaataaaatgaggaaattgcatcgcattgtctg agtaggtgtcattctattctggggggtggggtggggcaggacagcaagggggaggattgggaagacaatagcagggg ggtgggcgaagaactccagcatgagatccccgcgctggaggatcatccagccggcgtcccggaaaacgattccgaag cccaacctttcatagaaggcggcggtggaatcgaaatctcgtgatggcaggttgggcgtcgcttggtcggtcatttc gaaccccagagtcccgctcagaagaactcgtcaagaaggcgatagaaggcgatgcgctgcgaatcgggagcggcgat accgtaaagcacgaggaagcggtcagcccattcgccgccaagctcttcagcaatatcacgggtagccaacgctatgt cctgatagcggtccgccacacccagccggccacagtcgatgaatccagaaaagcggccattttccaccatgatattc ggcaagcaggcatcgccatgggtcacgacgagatcctcgccgtcgggcatgcgcgccttgagcctggcgaacagttc ggctggcgcgagcccctgatgctcttcgtccagatcatcctgatcgacaagaccggcttccatccgagtacgtgctc gctcgatgcgatgtttcgcttggtggtcgaatgggcaggtagccggatcaagcgtatgcagccgccgcattgcatca gccatgatggatactttctcggcaggagcaaggtgagatgacaggagatcctgccccggcacttcgcccaatagcag ccagtcccttcccgcttcagtgacaacgtcgagcacagctgcgcaaggaacgcccgtcgtggccagccacgatagcc gcgctgcctcgtcctgcagttcattcagggcaccggacaggtcggtcttgacaaaaagaaccgggcgcccctgcgct gacagccggaacacggcggcatcagagcagccgattgtctgttgtgcccagtcatagccgaatagcctctccaccca agcggccggagaacctgcgtgcaatccatcttgttcaatcatgcgaaacgatcctcatcctgtctcttgatcagatc ttagtcccctgcgccatcagatccttggcggcaagaaagccatccagtttactttgcagggcttcccaaccttacca gagggcgccccagctggcaattccggttcgcttgctgtccataaaaccgcccagtctagctatcgccatgtaagccc actgcaagctacctgctttctctttgcgcttgcgttttcccttgtccagatagcccagtagctgacattcatccggg gtcagcaccgtttctgcggactggctttctacgtgttccgcttcctttagcagcccttgcgccctgagtgcttgcgg cagcgtgaagctaattcatggttaaatttttgttaaatcagctcattttttaaccaataggccgaaatcggcaaaat cccttataaatcaaaagaatagcccgagatagggttgagtgttgttccagtttggaacaagagtccactattaaaga acgtggactccaacgtcaaagggcgaaaaaccgtctatcagggcgatggccggatcagcttatgcggtgtgaaatac cgcacagatgcgtaaggagaaaataccgcatcaggcgctcttccgcttcctcgctcactgactcgctgcgctcggtc gttcggctgcggcgagcggtatcagctcactcaaaggcggtaatacggttatccacagaatcaggggataacgcagg aaagaacatgtgagcaaaaggccagcaaaaggccaggaaccgtaaaaaggccgcgttgctggcgtttttccataggc tccgcccccctgacgagcatcacaaaaatcgacgctcaagtcagaggtggcgaaacccgacaggactataaagatac caggcgtttccccctggaagctccctcgtgcgctctcctgttccgaccctgccgcttaccggatacctgtccgcctt tctcccttcgggaagcgtggcgctttctcatagctcacgctgtaggtatctcagttcggtgtaggtcgttcgctcca agctgggctgtgtgcacgaaccccccgttcagcccgaccgctgcgccttatccggtaactatcgtcttgagtccaac ccggtaagacacgacttatcgccactggcagcagccactggtaacaggattagcagagcgaggtatgtaggcggtgc tacagagttcttgaagtggtggcctaactacggctacactagaaggacagtatttggtatctgcgctctgctgaagc cagttaccttcggaaaaagagttggtagctcttgatccggcaaacaaaccaccgctggtagcggtggtttttttgtt tgcaagcagcagattacgcgcagaaaaaaaggatctcaagaagatcctttgatcttttctactgaacggtgatcccc accggaattgcg (gH mature protein consisting of amino acid residues 24-715 of SEQ ID NO: 1) SEQ ID NO: 29 RYGAEAVSEPLDKAFHLLLNTYGRPIRFLRENTTQCTYNSSLPNSTVVRENAISFNFFQSYNQYYVFHMPRCLFAGP LAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQLKAQDSLGEQPTTVPPPIDLSIPHVWMPPQTTPHGW TESHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTEDFFVVTVSEDDDTPMLLIFGHLP RVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLDLSALLRNSFHRYAVDVLKSGRCQ MLDRRTVEMAPAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITCLSQTPPRTTLLLYPTAVDLAKRALW TPNQITDITSLVRLVYILSKQNQQHLIPQWALRQIADFALKLHKTHLASFLSAFARQELYLMGSLVHSMLVHTTERP EIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDHSLERLTRLFPDATVPATVPAALSILSTMQPST LETFPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVSTTVVGQSLIITQTDSQTKCELTRNMHTTHSITVA LNISLENCAFCQSALLEYDDYQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTHYLMLLKNGTVLEVTDVVVDATD (gH mature protein comprising SEQ ID NOs: 29 and 5) SEQ ID NO: 30 RYGAEAVSEPLDKAFHLLLNTYGRPIRFLRENTTQCTYNSSLRNSTVVRENAISFNFFQSYNQYYVFHMPRCLFAGP LAEQFLNQVDLTETLERYQQRLNTYALVSKDLASYRSFSQQLKAQDSLGEQPTTVPPPIDLSIPHVWMPPQTTPHGW TESHTTSGLHRPHFNQTCILFDGHDLLFSTVTPCLHQGFYLIDELRYVKITLTEDFFVVTVSIDDDTPMLLIFGHLP RVLFKAPYQRDNFILRQTEKHELLVLVKKDQLNRHSYLKDPDFLDAALDFNYLDLSALLRNSFHRYAVDVLKSGRCQ MLDRRTVEMAFAYALALFAAARQEEAGAQVSVPRALDRQAALLQIQEFMITCLSQTPPRTTLLLYPTAVDLAKRALW TPNQITDITSLVRLVYILSKQNQQHLIPQWALRQIADFALKLHKTHLASFLSAFARQELYLMGSLVHSMLVHTTERR EIFIVETGLCSLAELSHFTQLLAHPHHEYLSDLYTPCSSSGRRDHSLERLTRLFPDATVPATVPAALSILSTMQPST LETFPDLFCLPLGESFSALTVSEHVSYIVTNQYLIKGISYPVSTTVVGQSLIITQTDSQTKCELTRNMHTTHSITVA LNIDLRNCAFCQSALLEYDDTQGVINIMYMHDSDDVLFALDPYNEVVVSSPRTHYLMLLKNGTVLEVTDVVVDATDG TKLGPEQKLISEEDLNSAVDHHHHHH (gL mature protein consisting of amino acid residues 31-278 of SEQ ID NO: 7) SEQ ID NO: 31 AAVSVAPTAAEKVPAECPELTRRCLLGEVFEGDKYESWLRPLVNVTGRDGPLSQLIRYRPVTPEAASNVLLDEAFLD TLALLYNNPDQLRALLTLLSSDTAPRWMTVMRGYSECGDGSEAVYTCVDDLCRGYDLTRLSYGRSIFTEHVLGFELV PPSLFNVVVAIRNEATRTNRAVRLPVSTAAAPEGITLFYGLYNAVKEFCLRHQLDPPLLRHLDKYYAGLPPELKQTR VNLPAHSRYGPQAVDAR (gO mature protein consisting of amino acid residues 31-472 of SEQ ID NO: 10) SEQ ID NO: 32 CNVLVNSRGTRRSWPYTVLSYRGKEILKKQKEDILKRLMSTSSDGYRFLMYPSQQKFHAIVISMDKFPQDYILAGPI RNDSITHMWFDFYSTQLRKPAKYVYSEYNHTAHKITLRPPPCGTVPSMNCLSEMLNVSKRNDTGEKGCGNFTTFNPM FFNVPRWNTKLYIGSNKVNVDSQTIYFLGLTALLLRYAQRNCTRSFYLVNAMSRNLFRVPKYINGTKLKNTMRKLKR KQALVKEQPQKKNKKSQSTTTPYLSYTTSTAFNVTTNVTYSATAAVTYVATSTTGYRPDSNFMKSIMATQLRDLATW VYTTLRYRNEPFCKPDRNRTAVSEFMKNTHVLIRNETPYTIYGTLDMSSLYYNETMSVENETASDNNETTPTSPSTR FQRTFIDPLWDYLDSLLFLDKIRNFSLQLPAYGNLTPPEHRRAANLSTLNSLWWWSQ (pUL128 mature protein consisting of amino acid residues 28-171 of SEQ ID NO: 14 and 15) SEQ ID NO: 33 EECCEFINVNHPPERCYDFKMCNRFTVALRCPDGEVCYSPEKTAEIRGIVTTMTHSLTPQVVHNKLTSCNYNPLYLE ADGRIRCGKVNDKAQYLLGAAGSVPYRWINLEYDKITRIVGLDQYLESVKKHKRLDVCRAKMGYMLQ (pUL130 matare protein consisting of amino acid residues 26-214 of SEQ ID. NO: 16) SEQ ID NO: 34 SPWSTLTANQNPSPPWSKLTYSKPHDAATFYCPFLYPSPPRSPLQFSGFQRVSTGPECRNETLYLLYNREGQTLVER SSTWVKKVIWYLSGRNQTILQRMPRTASKPSDGNVQISVEDAKIFGAHMVPKQTKLLRFVVNDGTRYQMCVMKLESW AHVFRDYSVSFQVRLTFTEANNQTYTFCTHPNLIV (pUL131A mature protein consisting of amino acid residuess 19-129 of SEQ ID NO: 18 and SEQ ID NO: 19) SEQ ID NO: 35 QCQRETAEKNDYYRVPHYWDACSRALPDQTRYKYVEQLVDLTLNYHYDASHGLDNFDVLKRINVTEVSLLISDFRRQ NRRGGTNKRTTFNAAGSLAPHARSLEFSVRLFAN (gB mature protein consisting of amino acid residues 23-907 of SEQ ID NO: 21) SEQ ID NO: 36 VSSSSTRGTSATHSHHSSHTTSAAHSRSGSVSQRVTSSQTVSHGHNETIYNTTLKYGDVVGVNTTKYPYRVCSMAQG TDLIRFERNIVCTSMKPINEDLDEGIMVVYKRNIVAHTFKVRVYQKVLTFRRSYAYIRTTYLLGSNTEYVAPPMWEI HHINSHSQCYSSYSRVIAGTVFVAYHRDSYENKTMQLMPDDYSNTHSTRYVTVKDQWHSRGSTWLYRETCNLNCMVT ITTARSKYPYHFFATSTGDVVDISPPYNGTNRNASYFGENADKFFIFPNYTIVSDFGRPNSALETHRLVAFLERADS VISQDIQDEKNVTCQLTFWEASERTITSEAEDSYHFSSAKMTATFLSKKQEVNMSDSALDCVPDEAINKLQQIFNTS YNQTYEKYGNVSVFETTGGLVVFWQGIKQKSLVELERLANRSSLNLTHNRTYPSTDGNNATHLSNMESVHNLVYAQL QFTYDTLRGYINRALAQIAEAWCVDQRRTLEVFKELSKINPSAILSAIYNKPIAARFMGDVLGLASCVTINQTSVKV LRDMNVKESPGRCYSRPVVIFNFANSSYVQYGQLGEDKEILLGNHRTEECQLPSLKIFIAGNSAYEYVDYLFKRMID LSSISTVDSMIALDIDIPLENTDFRVLLYSQKELRSSNVFDLEEIMREFNSYKQRVKYVEDKVVDPLPPYLKGLDDL MSGLGAAGKAVGVAIGAVGGAVASVVEGVATFLKNPFGAFTIILVAIAVVIITYLIYTRQRRLCTQPLQNLFPYLVS ADGTTVTSGSTKDTSLQAPPSYEESVYNSGRKGPGPPSSDASTAAPPYTNEQAYQMLLALARLDAEQRAQQNGTDSL DGRTGTQDKGQKPNLLDRLRHRKNGYRHLKDSDEEENV