Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jul;87(14):5558–5562. doi: 10.1073/pnas.87.14.5558

Vaccination with a live retrovirus: the nature of the protective immune response.

R M Ruprecht 1, S Mullaney 1, L D Bernard 1, M A Gama Sosa 1, R C Hom 1, R W Finberg 1
PMCID: PMC54364  PMID: 2371289

Abstract

We tested 3'-azido-3'-deoxythymidine (zidovudine) combined with interferon alpha as chemoprophylaxis after exposing mice to Rauscher murine leukemia virus. Therapy started 4 hr after inoculation and administered for 20 days prevented viremia and disease in all 234 mice tested. When the animals were rechallenged with live virus after cessation of therapy, 96% were resistant. The nature of this protective immune response was analyzed: Passive serotherapy of naive mice challenged subsequently with Rauscher murine leukemia virus was only protective at a high dose of immune serum. Immune, but not naive, T cells alone were fully protective against virus challenge. We conclude that vaccination with a live retrovirus that cannot replicate because of pharmacological blockade induces a T-cell response capable of protecting against a lethal retrovirus-induced disease.

Full text

PDF
5558

Images in this article

5560Image
on p.5560
5560Image
on p.5560
5560Image
on p.5560
5560Image
on p.5560
5561Image
on p.5561

Selected References

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

  1. Ali M., Baluda M. A. Synthesis of avian oncornavirus DNA in infected chicken cells. J Virol. 1974 May;13(5):1005–1013. doi: 10.1128/jvi.13.5.1005-1013.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bolognesi D. P. AIDS. Do antibodies enhance the infection of cells by HIV? Nature. 1989 Aug 10;340(6233):431–432. doi: 10.1038/340431a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Braciale T. J., Yap K. L. Role of viral infectivity in the induction of influenza virus-specific cytotoxic T cells. J Exp Med. 1978 Apr 1;147(4):1236–1252. doi: 10.1084/jem.147.4.1236. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. CHIRIGOS M. A. STUDIES WITH THE MURINE LEUKEMOGENIC RAUSCHER VIRUS. 3. AN IN VIVO ASSAY FOR ANTI-VIRAL AGENTS. Cancer Res. 1964 Jul;24:1035–1041. [PubMed] [Google Scholar]
  5. Desrosiers R. C., Wyand M. S., Kodama T., Ringler D. J., Arthur L. O., Sehgal P. K., Letvin N. L., King N. W., Daniel M. D. Vaccine protection against simian immunodeficiency virus infection. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6353–6357. doi: 10.1073/pnas.86.16.6353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Earl P. L., Moss B., Morrison R. P., Wehrly K., Nishio J., Chesebro B. T-lymphocyte priming and protection against Friend leukemia by vaccinia-retrovirus env gene recombinant. Science. 1986 Nov 7;234(4777):728–731. doi: 10.1126/science.3490689. [DOI] [PubMed] [Google Scholar]
  7. FINK M. A., RAUSCHER F. J. IMMUNE REACTIONS TO A MURINE LEUKEMIA VIRUS. I. INDUCTION OF IMMUNITY TO INFECTION WITH VIRUS IN THE NATURAL HOST. J Natl Cancer Inst. 1964 May;32:1075–1082. [PubMed] [Google Scholar]
  8. FRIEND C. Immunological relationships of a filterable agent causing a leukemia in adult mice. I. The neutralization of infectivity by specific antiserum. J Exp Med. 1959 Feb 1;109(2):217–228. doi: 10.1084/jem.109.2.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hartshorn K. L., Vogt M. W., Chou T. C., Blumberg R. S., Byington R., Schooley R. T., Hirsch M. S. Synergistic inhibition of human immunodeficiency virus in vitro by azidothymidine and recombinant alpha A interferon. Antimicrob Agents Chemother. 1987 Feb;31(2):168–172. doi: 10.1128/aac.31.2.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Homsy J., Meyer M., Tateno M., Clarkson S., Levy J. A. The Fc and not CD4 receptor mediates antibody enhancement of HIV infection in human cells. Science. 1989 Jun 16;244(4910):1357–1360. doi: 10.1126/science.2786647. [DOI] [PubMed] [Google Scholar]
  11. Hunsmann G., Schneider J., Schulz A. Immunoprevention of Friend virus-induced erythroleukemia by vaccination with viral envelope glycoprotein complexes. Virology. 1981 Sep;113(2):602–612. doi: 10.1016/0042-6822(81)90188-4. [DOI] [PubMed] [Google Scholar]
  12. Lawman M. J., Rouse B. T., Courtney R. J., Walker R. D. Cell-mediated immunity against herpes simplex induction of cytotoxic T lymphocytes. Infect Immun. 1980 Jan;27(1):133–139. doi: 10.1128/iai.27.1.133-139.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marx P. A., Pedersen N. C., Lerche N. W., Osborn K. G., Lowenstine L. J., Lackner A. A., Maul D. H., Kwang H. S., Kluge J. D., Zaiss C. P. Prevention of simian acquired immune deficiency syndrome with a formalin-inactivated type D retrovirus vaccine. J Virol. 1986 Nov;60(2):431–435. doi: 10.1128/jvi.60.2.431-435.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Murphey-Corb M., Martin L. N., Davison-Fairburn B., Montelaro R. C., Miller M., West M., Ohkawa S., Baskin G. B., Zhang J. Y., Putney S. D. A formalin-inactivated whole SIV vaccine confers protection in macaques. Science. 1989 Dec 8;246(4935):1293–1297. doi: 10.1126/science.2555923. [DOI] [PubMed] [Google Scholar]
  15. Nobis P., Jaenisch R. Passive immunotherapy prevents expression of endogenous Moloney virus and amplification of proviral DNA in BALB/Mo mice. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3677–3681. doi: 10.1073/pnas.77.6.3677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Robinson W. E., Jr, Montefiori D. C., Gillespie D. H., Mitchell W. M. Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release. J Acquir Immune Defic Syndr. 1989;2(1):33–42. [PubMed] [Google Scholar]
  17. Robinson W. E., Jr, Montefiori D. C., Mitchell W. M. Antibody-dependent enhancement of human immunodeficiency virus type 1 infection. Lancet. 1988 Apr 9;1(8589):790–794. doi: 10.1016/s0140-6736(88)91657-1. [DOI] [PubMed] [Google Scholar]
  18. Rosenberg Z. F., Fauci A. S. The immunopathogenesis of HIV infection. Adv Immunol. 1989;47:377–431. doi: 10.1016/s0065-2776(08)60665-3. [DOI] [PubMed] [Google Scholar]
  19. Rowe W. P., Pugh W. E., Hartley J. W. Plaque assay techniques for murine leukemia viruses. Virology. 1970 Dec;42(4):1136–1139. doi: 10.1016/0042-6822(70)90362-4. [DOI] [PubMed] [Google Scholar]
  20. Ruprecht R. M., Chou T. C., Chipty F., Sosa M. G., Mullaney S., O'Brien L., Rosas D. Interferon-alpha and 3'-azido-3'-deoxythymidine are highly synergistic in mice and prevent viremia after acute retrovirus exposure. J Acquir Immune Defic Syndr. 1990;3(6):591–600. [PubMed] [Google Scholar]
  21. Ruprecht R. M., Gama-Sosa M. A., Rosas H. D. Combination therapy after retroviral inoculation. Lancet. 1988 Jan 30;1(8579):239–240. doi: 10.1016/s0140-6736(88)91087-2. [DOI] [PubMed] [Google Scholar]
  22. Ruprecht R. M., O'Brien L. G., Rossoni L. D., Nusinoff-Lehrman S. Suppression of mouse viraemia and retroviral disease by 3'-azido-3'-deoxythymidine. Nature. 1986 Oct 2;323(6087):467–469. doi: 10.1038/323467a0. [DOI] [PubMed] [Google Scholar]
  23. Ruprecht R. M., Rossoni L. D., Haseltine W. A., Broder S. Suppression of retroviral propagation and disease by suramin in murine systems. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7733–7737. doi: 10.1073/pnas.82.22.7733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Sarma P. S., Rowe W. P. Mouse immunoglobulin antibodies require complement for neutralization of mouse retroviruses. J Virol. 1983 Mar;45(3):956–960. doi: 10.1128/jvi.45.3.956-960.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schumacher C. L., Dietzschold B., Ertl H. C., Niu H. S., Rupprecht C. E., Koprowski H. Use of mouse anti-rabies monoclonal antibodies in postexposure treatment of rabies. J Clin Invest. 1989 Sep;84(3):971–975. doi: 10.1172/JCI114260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Takeda A., Tuazon C. U., Ennis F. A. Antibody-enhanced infection by HIV-1 via Fc receptor-mediated entry. Science. 1988 Oct 28;242(4878):580–583. doi: 10.1126/science.2972065. [DOI] [PubMed] [Google Scholar]
  27. Varmus H. E., Vogt P. K., Bishop J. M. Integration of deoxyribonucleic acid specific for Rous sarcoma virus after infection of permissive and nonpermissive hosts. Proc Natl Acad Sci U S A. 1973 Nov;70(11):3067–3071. doi: 10.1073/pnas.70.11.3067. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES