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. 1985 Dec;56(3):930–937. doi: 10.1128/jvi.56.3.930-937.1985

Passive immune protection by herpes simplex virus-specific monoclonal antibodies and monoclonal antibody-resistant mutants altered in pathogenicity.

G Kümel, H C Kaerner, M Levine, C H Schröder, J C Glorioso
PMCID: PMC252666  PMID: 2415719

Abstract

Virus-neutralizing monoclonal antibodies specific for 13 different genetically defined epitopes of glycoproteins gC, gB, and gD of herpes simplex virus type 1, strain KOS-321, were compared for their ability to provide passive immunity to DBA-2 mice challenged intracranially. Protection was highly specific, since individual monoclonal antibodies failed to protect against infection with monoclonal antibody-resistant (mar) mutants altered in the single epitope recognized by the injected antibody. The dose-response kinetics of passive immunity paralleled the in vitro neutralization titers for each antibody. No correlation was observed between immune protection and antibody isotype or complement-dependent in vitro neutralization titers. This suggests that virus neutralization was not the protective mechanism. In general, antibodies reactive with epitopes of gC were protective at the lowest antibody doses, antibodies specific for gB were less efficient in providing immunity, and antibodies against gD were the least effective. mar mutants with single epitope changes in gC and multiple epitope changes in gB showed highly reduced pathogenicity, requiring up to 5 X 10(6) PFU to kill 50% of infected animals. These findings indicated that antigenic variation affects virus growth and spread in the central nervous system. Thus, mutations which affect antigenic structure also can alter virus pathogenicity. The alteration of these epitopes does not, however, appreciably reduce the development of resistance to infection. Infection of mice with these mutants or inoculation of mice with UV-inactivated, mutant-infected cells before challenge rendered the animals resistant to infection with wild-type herpes simplex virus type 1.

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Selected References

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  1. Balachandran N., Bacchetti S., Rawls W. E. Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun. 1982 Sep;37(3):1132–1137. doi: 10.1128/iai.37.3.1132-1137.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Berden J. H., Bogman M. J., Hagemann F. H., Tamboer W. P., Koene R. A. Complement-dependent and independent mechanisms in acute antibody-mediated rejection of skin xenografts in the mouse. Transplantation. 1981 Oct;32(4):265–270. doi: 10.1097/00007890-198110000-00001. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Cohen G. H., Dietzschold B., Ponce de Leon M., Long D., Golub E., Varrichio A., Pereira L., Eisenberg R. J. Localization and synthesis of an antigenic determinant of herpes simplex virus glycoprotein D that stimulates the production of neutralizing antibody. J Virol. 1984 Jan;49(1):102–108. doi: 10.1128/jvi.49.1.102-108.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davis W. B., Taylor J. A., Oakes J. E. Ocular infection with herpes simplex virus type 1: prevention of acute herpetic encephalitis by systemic administration of virus-specific antibody. J Infect Dis. 1979 Oct;140(4):534–540. doi: 10.1093/infdis/140.4.534. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Eisenberg R. J., Long D., Ponce de Leon M., Matthews J. T., Spear P. G., Gibson M. G., Lasky L. A., Berman P., Golub E., Cohen G. H. Localization of epitopes of herpes simplex virus type 1 glycoprotein D. J Virol. 1985 Feb;53(2):634–644. doi: 10.1128/jvi.53.2.634-644.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Glorioso J., Schröder C. H., Kumel G., Szczesiul M., Levine M. Immunogenicity of herpes simplex virus glycoproteins gC and gB and their role in protective immunity. J Virol. 1984 Jun;50(3):805–812. doi: 10.1128/jvi.50.3.805-812.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Glorioso J., Szczesiul M. S., Marlin S. D., Levine M. Inhibition of glycosylation of herpes simplex virus glycoproteins: identification of antigenic and immunogenic partially glycosylated glycopeptides on the cell surface membrane. Virology. 1983 Apr 15;126(1):1–18. doi: 10.1016/0042-6822(83)90458-0. [DOI] [PubMed] [Google Scholar]
  11. Holland T. C., Homa F. L., Marlin S. D., Levine M., Glorioso J. Herpes simplex virus type 1 glycoprotein C-negative mutants exhibit multiple phenotypes, including secretion of truncated glycoproteins. J Virol. 1984 Nov;52(2):566–574. doi: 10.1128/jvi.52.2.566-574.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Holland T. C., Marlin S. D., Levine M., Glorioso J. Antigenic variants of herpes simplex virus selected with glycoprotein-specific monoclonal antibodies. J Virol. 1983 Feb;45(2):672–682. doi: 10.1128/jvi.45.2.672-682.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holland T. C., Sandri-Goldin R. M., Holland L. E., Marlin S. D., Levine M., Glorioso J. C. Physical mapping of the mutation in an antigenic variant of herpes simplex virus type 1 by use of an immunoreactive plaque assay. J Virol. 1983 May;46(2):649–652. doi: 10.1128/jvi.46.2.649-652.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kapoor A. K., Nash A. A., Wildy P., Phelan J., McLean C. S., Field H. J. Pathogenesis of herpes simplex virus in congenitally athymic mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol. 1982 Jun;60(Pt 2):225–233. doi: 10.1099/0022-1317-60-2-225. [DOI] [PubMed] [Google Scholar]
  15. Kousoulas K. G., Pellett P. E., Pereira L., Roizman B. Mutations affecting conformation or sequence of neutralizing epitopes identified by reactivity of viable plaques segregate from syn and ts domains of HSV-1(F) gB gene. Virology. 1984 Jun;135(2):379–394. doi: 10.1016/0042-6822(84)90194-6. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Marlin S. D., Holland T. C., Levine M., Glorioso J. C. Epitopes of herpes simplex virus type 1 glycoprotein gC are clustered in two distinct antigenic sites. J Virol. 1985 Jan;53(1):128–136. doi: 10.1128/jvi.53.1.128-136.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pereira L., Dondero D. V., Gallo D., Devlin V., Woodie J. D. Serological analysis of herpes simplex virus types 1 and 2 with monoclonal antibodies. Infect Immun. 1982 Jan;35(1):363–367. doi: 10.1128/iai.35.1.363-367.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rawls W. E., Balachandran N., Sisson G., Watson R. J. Localization of a type-specific antigenic site on herpes simplex virus type 2 glycoprotein D. J Virol. 1984 Jul;51(1):263–265. doi: 10.1128/jvi.51.1.263-265.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Rector J. T., Lausch R. N., Oakes J. E. Use of monoclonal antibodies for analysis of antibody-dependent immunity to ocular herpes simplex virus type 1 infection. Infect Immun. 1982 Oct;38(1):168–174. doi: 10.1128/iai.38.1.168-174.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Schröeder C. H., Engler H., Kirchner H. Protection of mice by an apathogenic strain HSV-1 against lethal infection by a pathogenic strain of HSV-1. J Gen Virol. 1981 Jan;52(Pt 1):159–161. doi: 10.1099/0022-1317-52-1-159. [DOI] [PubMed] [Google Scholar]
  23. Yewdell J. W., Gerhard W. Antigenic characterization of viruses by monoclonal antibodies. Annu Rev Microbiol. 1981;35:185–206. doi: 10.1146/annurev.mi.35.100181.001153. [DOI] [PubMed] [Google Scholar]

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