Skip to main content

Some NLM-NCBI services and products are experiencing heavy traffic, which may affect performance and availability. We apologize for the inconvenience and appreciate your patience. For assistance, please contact our Help Desk at info@ncbi.nlm.nih.gov.

Journal of Virology logoLink to Journal of Virology
. 1985 Nov;56(2):475–481. doi: 10.1128/jvi.56.2.475-481.1985

Humoral immune response to herpes simplex virus type 2 glycoproteins in patients receiving a glycoprotein subunit vaccine.

R Ashley, G Mertz, H Clark, M Schick, D Salter, L Corey
PMCID: PMC252602  PMID: 2997470

Abstract

Serial serum specimens from 22 herpes simplex virus (HSV)-seronegative recipients of an HSV type 2 (HSV-2) glycoprotein subunit vaccine were analyzed by radioimmunoprecipitation and polyacrylamide gel electrophoresis for the development of antibodies to HSV-2 gB, gD, and g80, a complex of gC and gE. Volunteers received 50 (n = 12) or 100 micrograms (n = 10) of vaccine at days 0, 28, and 140; sera were drawn weekly for 8 weeks and again at days 140, 147, and 365. Among seronegative volunteers, antibody to gB was detected 2 weeks after the first dose, while antibodies to g80 and gD were detected after the second dose (day 35). Antibodies to nonglycosylated HSV-specific proteins were not detected. A dose-response effect between recipients of 50- and 100-micrograms doses was observed in the proportion of vaccine recipients seroconverting to g80 and in the proportion of recipients retaining antibodies to both gD and g80 over time. Diminishing complement-independent neutralizing antibody titers occurred after the second dose and were associated with loss or reduction of detectable antibody to gD. Volunteers who were seropositive for HSV-1-specific antibody (n = 11) were also enrolled in the trial and received 50-micrograms doses of vaccine. Vaccination resulted in conversion to HSV-2 complement-independent neutralizing antibody specificity or indeterminant specificity in 10 of 11 volunteers. These shifts were accompanied by changes in the radioimmunoprecipitation and polyacrylamide gel electrophoresis profile. These changes, which were apparent by 14 days after the first vaccine dose, included de novo appearance or increased levels of antibody to g80 and increased levels of antibody to gD and gB. These studies document the immunogenicity of solubilized glycoproteins gB, gD, gC, and, possibly, gE in humans.

Full text

PDF
475

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arvin A. M., Koropchak C. M., Yeager A. S., Pereira L. Detection of type-specific antibody to herpes simplex virus type 1 by radioimmunoassay with herpes simplex virus type 1 glycoprotein C purified with monoclonal antibody. Infect Immun. 1983 Apr;40(1):184–189. doi: 10.1128/iai.40.1.184-189.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ashley R. L., Corey L. Effect of acyclovir treatment of primary genital herpes on the antibody response to herpes simplex virus. J Clin Invest. 1984 Mar;73(3):681–688. doi: 10.1172/JCI111260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Balachandran N., Harnish D., Killington R. A., Bacchetti S., Rawls W. E. Monoclonal antibodies to two glycoproteins of herpes simplex virus type 2. J Virol. 1981 Aug;39(2):438–446. doi: 10.1128/jvi.39.2.438-446.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Balachandran N., Harnish D., Rawls W. E., Bacchetti S. Glycoproteins of herpes simplex virus type 2 as defined by monoclonal antibodies. J Virol. 1982 Oct;44(1):344–355. doi: 10.1128/jvi.44.1.344-355.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  6. Chamberlain J. P. Fluorographic detection of radioactivity in polyacrylamide gels with the water-soluble fluor, sodium salicylate. Anal Biochem. 1979 Sep 15;98(1):132–135. doi: 10.1016/0003-2697(79)90716-4. [DOI] [PubMed] [Google Scholar]
  7. Chan W. L. Protective immunization of mice with specific HSV-1 glycoproteins. Immunology. 1983 Jun;49(2):343–352. [PMC free article] [PubMed] [Google Scholar]
  8. Coleman R. M., Pereira L., Bailey P. D., Dondero D., Wickliffe C., Nahmias A. J. Determination of herpes simplex virus type-specific antibodies by enzyme-linked immunosorbent assay. J Clin Microbiol. 1983 Aug;18(2):287–291. doi: 10.1128/jcm.18.2.287-291.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Corey L., Adams H. G., Brown Z. A., Holmes K. K. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. 1983 Jun;98(6):958–972. doi: 10.7326/0003-4819-98-6-958. [DOI] [PubMed] [Google Scholar]
  10. Dix R. D., Pereira L., Baringer J. R. Use of monoclonal antibody directed against herpes simplex virus glycoproteins to protect mice against acute virus-induced neurological disease. Infect Immun. 1981 Oct;34(1):192–199. doi: 10.1128/iai.34.1.192-199.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eberle R., Mou S. W. Relative titers of antibodies to individual polypeptide antigens of herpes simplex virus type 1 in human sera. J Infect Dis. 1983 Sep;148(3):436–444. doi: 10.1093/infdis/148.3.436. [DOI] [PubMed] [Google Scholar]
  12. Eisenberg R. J., Ponce de Leon M., Cohen G. H. Comparative structural analysis of glycoprotein gD of herpes simplex virus types 1 and 2. J Virol. 1980 Aug;35(2):428–435. doi: 10.1128/jvi.35.2.428-435.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gershoni J. M., Palade G. E. Protein blotting: principles and applications. Anal Biochem. 1983 May;131(1):1–15. doi: 10.1016/0003-2697(83)90128-8. [DOI] [PubMed] [Google Scholar]
  14. Long D., Madara T. J., Ponce de Leon M., Cohen G. H., Montgomery P. C., Eisenberg R. J. Glycoprotein D protects mice against lethal challenge with herpes simplex virus types 1 and 2. Infect Immun. 1984 Feb;43(2):761–764. doi: 10.1128/iai.43.2.761-764.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marsden H. S., Buckmaster A., Palfreyman J. W., Hope R. G., Minson A. C. Characterization of the 92,000-dalton glycoprotein induced by herpes simplex virus type 2. J Virol. 1984 May;50(2):547–554. doi: 10.1128/jvi.50.2.547-554.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McKendall R. R., Klassen T., Baringer J. R. Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread. Infect Immun. 1979 Feb;23(2):305–311. doi: 10.1128/iai.23.2.305-311.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mertz G. J., Peterman G., Ashley R., Jourden J. L., Salter D., Morrison L., McLean A., Corey L. Herpes simplex virus type-2 glycoprotein-subunit vaccine: tolerance and humoral and cellular responses in humans. J Infect Dis. 1984 Aug;150(2):242–249. doi: 10.1093/infdis/150.2.242. [DOI] [PubMed] [Google Scholar]
  18. Nahmias A. J., Josey W. E., Naib Z. M., Luce C. F., Duffey A. Antibodies to Herpesvirus hominis types 1 and 2 in humans. I. Patients with genital herpetic infections. Am J Epidemiol. 1970 Jun;91(6):539–546. doi: 10.1093/oxfordjournals.aje.a121165. [DOI] [PubMed] [Google Scholar]
  19. Nahmias A. J., Roizman B. Infection with herpes-simplex viruses 1 and 2. 1. N Engl J Med. 1973 Sep 27;289(13):667–674. doi: 10.1056/NEJM197309272891305. [DOI] [PubMed] [Google Scholar]
  20. Norrild B., Shore S. L., Nahmias A. J. Herpes simplex virus glycoproteins: participation of individual herpes simplex virus type 1 glycoprotein antigens in immunocytolysis and their correlation with previously identified glycopolypeptides. J Virol. 1979 Dec;32(3):741–748. doi: 10.1128/jvi.32.3.741-748.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Openshaw H., Asher L. V., Wohlenberg C., Sekizawa T., Notkins A. L. Acute and latent infection of sensory ganglia with herpes simplex virus: immune control and virus reactivation. J Gen Virol. 1979 Jul;44(1):205–215. doi: 10.1099/0022-1317-44-1-205. [DOI] [PubMed] [Google Scholar]
  22. Para M. F., Goldstein L., Spear P. G. Similarities and differences in the Fc-binding glycoprotein (gE) of herpes simplex virus types 1 and 2 and tentative mapping of the viral gene for this glycoprotein. J Virol. 1982 Jan;41(1):137–144. doi: 10.1128/jvi.41.1.137-144.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Para M. F., Zezulak K. M., Conley A. J., Weinberger M., Snitzer K., Spear P. G. Use of monoclonal antibodies against two 75,000-molecular-weight glycoproteins specified by herpes simplex virus type 2 in glycoprotein identification and gene mapping. J Virol. 1983 Mar;45(3):1223–1227. doi: 10.1128/jvi.45.3.1223-1227.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pereira L., Klassen T., Baringer J. R. Type-common and type-specific monoclonal antibody to herpes simplex virus type 1. Infect Immun. 1980 Aug;29(2):724–732. doi: 10.1128/iai.29.2.724-732.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Price R. W., Walz M. A., Wohlenberg C., Notkins A. L. Latent infection of sensory ganglia with herpes simplex virus: efficacy of immunization. Science. 1975 May 30;188(4191):938–940. doi: 10.1126/science.166432. [DOI] [PubMed] [Google Scholar]
  26. Rawls W. E., Iwamoto K., Adam E., Melnick J. L. Measurement of antibodies to herpesvirus types 1 and 2 in human sera. J Immunol. 1970 Mar;104(3):599–606. [PubMed] [Google Scholar]
  27. Reeves W. C., Corey L., Adams H. G., Vontver L. A., Holmes K. K. Risk of recurrence after first episodes of genital herpes. Relation to HSV type and antibody response. N Engl J Med. 1981 Aug 6;305(6):315–319. doi: 10.1056/NEJM198108063050604. [DOI] [PubMed] [Google Scholar]
  28. Schrier R. D., Pizer L. I., Moorhead J. W. Type-specific delayed hypersensitivity and protective immunity induced by isolated herpes simplex virus glycoprotein. J Immunol. 1983 Mar;130(3):1413–1418. [PubMed] [Google Scholar]
  29. Sekizawa T., Openshaw H., Wohlenberg C., Notkins A. L. Latency of herpes simplex virus in absence of neutralizing antibody: model for reactivation. Science. 1980 Nov 28;210(4473):1026–1028. doi: 10.1126/science.6254149. [DOI] [PubMed] [Google Scholar]
  30. Stevens J. G., Cook M. L. Maintenance of latent herpetic infection: an apparent role for anti-viral IgG. J Immunol. 1974 Dec;113(6):1685–1693. [PubMed] [Google Scholar]
  31. Svennerholm B., Olofsson S., Jeansson S., Vahlne A., Lycke E. Herpes simplex virus type-selective enzyme-linked immunosorbent assay with Helix pomatia lectin-purified antigens. J Clin Microbiol. 1984 Feb;19(2):235–239. doi: 10.1128/jcm.19.2.235-239.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zezulak K. M., Spear P. G. Characterization of a herpes simplex virus type 2 75,000-molecular-weight glycoprotein antigenically related to herpes simplex virus type 1 glycoprotein C. J Virol. 1983 Sep;47(3):553–562. doi: 10.1128/jvi.47.3.553-562.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zweerink H. J., Corey L. Virus-specific antibodies in sera from patients with genital herpes simplex virus infection. Infect Immun. 1982 Aug;37(2):413–421. doi: 10.1128/iai.37.2.413-421.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zweig M., Showalter S. D., Bladen S. V., Heilman C. J., Jr, Hampar B. Herpes simplex virus type 2 glycoprotein gF and type 1 glycoprotein gC have related antigenic determinants. J Virol. 1983 Jul;47(1):185–192. doi: 10.1128/jvi.47.1.185-192.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES