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. 1995 Dec;69(12):8109–8113. doi: 10.1128/jvi.69.12.8109-8113.1995

Immunization with recombinant varicella-zoster virus expressing herpes simplex virus type 2 glycoprotein D reduces the severity of genital herpes in guinea pigs.

T C Heineman 1, B L Connelly 1, N Bourne 1, L R Stanberry 1, J Cohen 1
PMCID: PMC189763  PMID: 7494331

Abstract

Varicella-zoster virus (VZV) is an attractive candidate for a live-virus vector for the delivery of foreign antigens. The Oka vaccine strain of VZV is safe and effective in humans, and recombinant Oka VZV (ROka) can be generated by transfecting cells with a set of overlapping cosmid DNAs. By this method, the herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) gene was inserted into an intergenic site in the unique short region of the Oka VZV genome. Expression of gD2 in cells infected with the recombinant Oka strain VZV (ROka-gD2) was confirmed by antibody staining of fixed cells and by immunoblot analysis. Immune electron microscopy demonstrated the presence of gD2 in the envelope of ROka-gD2 virions. The ability of ROka-gD2 to protect guinea pigs against HSV-2 challenge was assessed by inoculating animals with three doses of uninfected human fibroblasts, fibroblasts infected with ROka VZV, or fibroblasts infected with ROka-gD2. Neutralizing antibodies specific for HSV-2 developed in animals immunized with ROka-gD2. Forty days after the third inoculation, animals were challenged intravaginally with HSV-2. Inoculation of guinea pigs with ROka-gD2 significantly reduced the severity of primary HSV-2 infection (P < 0.001). These experiments demonstrate that the Oka strain of VZV can be used as a live virus vector to protect animals from disease with a heterologous virus.

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Selected References

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  1. Arvin A. M., Solem S. M., Koropchak C. M., Kinney-Thomas E., Paryani S. G. Humoral and cellular immunity to varicella-zoster virus glycoprotein gpI and to a non-glycosylated protein, p170, in the strain 2 guinea-pig. J Gen Virol. 1987 Sep;68(Pt 9):2449–2454. doi: 10.1099/0022-1317-68-9-2449. [DOI] [PubMed] [Google Scholar]
  2. Berman P. W., Gregory T., Crase D., Lasky L. A. Protection from genital herpes simplex virus type 2 infection by vaccination with cloned type 1 glycoprotein D. Science. 1985 Mar 22;227(4693):1490–1492. doi: 10.1126/science.2983428. [DOI] [PubMed] [Google Scholar]
  3. Bernstein D. I., Stanberry L. R., Harrison C. J., Kappes J. C., Myers M. G. Antibody response, recurrence patterns and subsequent herpes simplex virus type 2 (HSV-2) re-infection following initial HSV-2 infection of guinea-pigs: effects of acyclovir. J Gen Virol. 1986 Aug;67(Pt 8):1601–1612. doi: 10.1099/0022-1317-67-8-1601. [DOI] [PubMed] [Google Scholar]
  4. Cohen G. H., Katze M., Hydrean-Stern C., Eisenberg R. J. Type-common CP-1 antigen of herpes simplex virus is associated with a 59,000-molecular-weight envelope glycoprotein. J Virol. 1978 Jul;27(1):172–181. doi: 10.1128/jvi.27.1.172-181.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cohen J. I., Seidel K. E. Absence of varicella-zoster virus (VZV) glycoprotein V does not alter growth of VZV in vitro or sensitivity to heparin. J Gen Virol. 1994 Nov;75(Pt 11):3087–3093. doi: 10.1099/0022-1317-75-11-3087. [DOI] [PubMed] [Google Scholar]
  6. Cohen J. I., Seidel K. E. Generation of varicella-zoster virus (VZV) and viral mutants from cosmid DNAs: VZV thymidylate synthetase is not essential for replication in vitro. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7376–7380. doi: 10.1073/pnas.90.15.7376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cohen J. I., Seidel K. E. Varicella-zoster virus open reading frame 1 encodes a membrane protein that is dispensable for growth of VZV in vitro. Virology. 1995 Feb 1;206(2):835–842. doi: 10.1006/viro.1995.1006. [DOI] [PubMed] [Google Scholar]
  8. Cohen J. I., Seidel K. Varicella-zoster virus (VZV) open reading frame 10 protein, the homolog of the essential herpes simplex virus protein VP16, is dispensable for VZV replication in vitro. J Virol. 1994 Dec;68(12):7850–7858. doi: 10.1128/jvi.68.12.7850-7858.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
  10. Fuller A. O., Lee W. C. Herpes simplex virus type 1 entry through a cascade of virus-cell interactions requires different roles of gD and gH in penetration. J Virol. 1992 Aug;66(8):5002–5012. doi: 10.1128/jvi.66.8.5002-5012.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Heineman T. C., Cohen J. I. Deletion of the varicella-zoster virus large subunit of ribonucleotide reductase impairs growth of virus in vitro. J Virol. 1994 May;68(5):3317–3323. doi: 10.1128/jvi.68.5.3317-3323.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Johnson R. M., Lancki D. W., Fitch F. W., Spear P. G. Herpes simplex virus glycoprotein D is recognized as antigen by CD4+ and CD8+ T lymphocytes from infected mice. Characterization of T cell clones. J Immunol. 1990 Jul 15;145(2):702–710. [PubMed] [Google Scholar]
  13. Kohl S., Strynadka N. C., Hodges R. S., Pereira L. Analysis of the role of antibody-dependent cellular cytotoxic antibody activity in murine neonatal herpes simplex virus infection with antibodies to synthetic peptides of glycoprotein D and monoclonal antibodies to glycoprotein B. J Clin Invest. 1990 Jul;86(1):273–278. doi: 10.1172/JCI114695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ligas M. W., Johnson D. C. A herpes simplex virus mutant in which glycoprotein D sequences are replaced by beta-galactosidase sequences binds to but is unable to penetrate into cells. J Virol. 1988 May;62(5):1486–1494. doi: 10.1128/jvi.62.5.1486-1494.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lowe R. S., Keller P. M., Keech B. J., Davison A. J., Whang Y., Morgan A. J., Kieff E., Ellis R. W. Varicella-zoster virus as a live vector for the expression of foreign genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3896–3900. doi: 10.1073/pnas.84.11.3896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McGeoch D. J., Moss H. W., McNab D., Frame M. C. DNA sequence and genetic content of the HindIII l region in the short unique component of the herpes simplex virus type 2 genome: identification of the gene encoding glycoprotein G, and evolutionary comparisons. J Gen Virol. 1987 Jan;68(Pt 1):19–38. doi: 10.1099/0022-1317-68-1-19. [DOI] [PubMed] [Google Scholar]
  17. Myers M. G., Connelly B. L. Animal models of varicella. J Infect Dis. 1992 Aug;166 (Suppl 1):S48–S50. doi: 10.1093/infdis/166.supplement_1.s48. [DOI] [PubMed] [Google Scholar]
  18. Myers M. G., Connelly B. L., Stanberry L. R. Varicella in hairless guinea pigs. J Infect Dis. 1991 Apr;163(4):746–751. doi: 10.1093/infdis/163.4.746. [DOI] [PubMed] [Google Scholar]
  19. Shiraki K., Hayakawa Y., Mori H., Namazue J., Takamizawa A., Yoshida I., Yamanishi K., Takahashi M. Development of immunogenic recombinant Oka varicella vaccine expressing hepatitis B virus surface antigen. J Gen Virol. 1991 Jun;72(Pt 6):1393–1399. doi: 10.1099/0022-1317-72-6-1393. [DOI] [PubMed] [Google Scholar]
  20. Stanberry L. R., Bernstein D. I., Burke R. L., Pachl C., Myers M. G. Vaccination with recombinant herpes simplex virus glycoproteins: protection against initial and recurrent genital herpes. J Infect Dis. 1987 May;155(5):914–920. doi: 10.1093/infdis/155.5.914. [DOI] [PubMed] [Google Scholar]
  21. Stanberry L. R., Burke R., Myers M. G. Herpes simplex virus glycoprotein treatment of recurrent genital herpes. J Infect Dis. 1988 Jan;157(1):156–163. doi: 10.1093/infdis/157.1.156. [DOI] [PubMed] [Google Scholar]
  22. Stanberry L. R., Kern E. R., Richards J. T., Abbott T. M., Overall J. C., Jr Genital herpes in guinea pigs: pathogenesis of the primary infection and description of recurrent disease. J Infect Dis. 1982 Sep;146(3):397–404. doi: 10.1093/infdis/146.3.397. [DOI] [PubMed] [Google Scholar]
  23. Straus S. E., Corey L., Burke R. L., Savarese B., Barnum G., Krause P. R., Kost R. G., Meier J. L., Sekulovich R., Adair S. F. Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet. 1994 Jun 11;343(8911):1460–1463. doi: 10.1016/s0140-6736(94)92581-x. [DOI] [PubMed] [Google Scholar]
  24. Straus S. E., Savarese B., Tigges M., Freifeld A. G., Krause P. R., Margolis D. M., Meier J. L., Paar D. P., Adair S. F., Dina D. Induction and enhancement of immune responses to herpes simplex virus type 2 in humans by use of a recombinant glycoprotein D vaccine. J Infect Dis. 1993 May;167(5):1045–1052. doi: 10.1093/infdis/167.5.1045. [DOI] [PubMed] [Google Scholar]
  25. Takahashi M. Current status and prospects of live varicella vaccine. Vaccine. 1992;10(14):1007–1014. doi: 10.1016/0264-410x(92)90109-w. [DOI] [PubMed] [Google Scholar]
  26. Wachsman M., Aurelian L., Smith C. C., Lipinskas B. R., Perkus M. E., Paoletti E. Protection of guinea pigs from primary and recurrent herpes simplex virus (HSV) type 2 cutaneous disease with vaccinia virus recombinants expressing HSV glycoprotein D. J Infect Dis. 1987 Jun;155(6):1188–1197. doi: 10.1093/infdis/155.6.1188. [DOI] [PubMed] [Google Scholar]
  27. Watson R. J. DNA sequence of the Herpes simplex virus type 2 glycoprotein D gene. Gene. 1983 Dec;26(2-3):307–312. doi: 10.1016/0378-1119(83)90203-2. [DOI] [PubMed] [Google Scholar]

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