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. 1997 Mar;71(3):1911–1921. doi: 10.1128/jvi.71.3.1911-1921.1997

Rhesus macaques previously infected with simian/human immunodeficiency virus are protected from vaginal challenge with pathogenic SIVmac239.

C J Miller 1, M B McChesney 1, X Lü 1, P J Dailey 1, C Chutkowski 1, D Lu 1, P Brosio 1, B Roberts 1, Y Lu 1
PMCID: PMC191267  PMID: 9032322

Abstract

Nontraumatic vaginal inoculation of rhesus macaques with a simian/human immunodeficiency virus (SIV/HIV) chimera containing the envelope gene from HIV-1 89.6 (SHIV 89.6) results in systemic infection (Y. Lu, B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045-3050, 1996). A total of five rhesus macaques have each been infected by exposure to at least three intravaginal inoculations of SHIV 89.6. The SHIV 89.6 infection is characterized by a transient viremia that evokes humoral and cellular immune responses to HIV and SIV antigens, but disease does not develop in animals infected with SHIV 89.6. To determine if a previous infection with SHIV 89.6 by vaginal inoculation could protect animals from vaginal challenge with pathogenic SIV, all five animals were intravaginally inoculated twice with pathogenic SIV-mac239. After challenge, all of the SHIV-immunized animals had low or undetectable viral RNA levels in plasma compared to control animals. Three of the five of the SHIV-immunized animals remained virus isolation negative for more than 8 months, while two became virus isolation positive. The presence of SIV Gag-specific cytotoxic T lymphocytes in peripheral blood mononuclear cells and SIV-specific antibodies in cervicovaginal secretions at the time of challenge was associated with resistance to pathogenic SIV infection after vaginal challenge. These results suggest that protection from sexual transmission of HIV may be possible by effectively stimulating both humoral and cellular antiviral immunity in the systemic and genital mucosal immune compartments.

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Selected References

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  1. Ahmad S., Lohman B., Marthas M., Giavedoni L., el-Amad Z., Haigwood N. L., Scandella C. J., Gardner M. B., Luciw P. A., Yilma T. Reduced virus load in rhesus macaques immunized with recombinant gp160 and challenged with simian immunodeficiency virus. AIDS Res Hum Retroviruses. 1994 Feb;10(2):195–204. doi: 10.1089/aid.1994.10.195. [DOI] [PubMed] [Google Scholar]
  2. Archibald D. W., Witt D. J., Craven D. E., Vogt M. W., Hirsch M. S., Essex M. Antibodies to human immunodeficiency virus in cervical secretions from women at risk for AIDS. J Infect Dis. 1987 Jul;156(1):240–241. doi: 10.1093/infdis/156.1.240. [DOI] [PubMed] [Google Scholar]
  3. Belec L., Georges A. J., Steenman G., Martin P. M. Antibodies to human immunodeficiency virus in vaginal secretions of heterosexual women. J Infect Dis. 1989 Sep;160(3):385–391. doi: 10.1093/infdis/160.3.385. [DOI] [PubMed] [Google Scholar]
  4. Bogers W. M., Niphuis H., ten Haaft P., Laman J. D., Koornstra W., Heeney J. L. Protection from HIV-1 envelope-bearing chimeric simian immunodeficiency virus (SHIV) in rhesus macaques infected with attenuated SIV: consequences of challenge. AIDS. 1995 Dec;9(12):F13–F18. [PubMed] [Google Scholar]
  5. Bélec L., Tévi-Bénissan C., Grésenguet G., Meillet D., Pillot J. HIV-1 antibody serum negativity with vaginal secretions positivity. Lancet. 1994 Apr 23;343(8904):1046–1047. doi: 10.1016/s0140-6736(94)90168-6. [DOI] [PubMed] [Google Scholar]
  6. Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
  7. Collman R., Balliet J. W., Gregory S. A., Friedman H., Kolson D. L., Nathanson N., Srinivasan A. An infectious molecular clone of an unusual macrophage-tropic and highly cytopathic strain of human immunodeficiency virus type 1. J Virol. 1992 Dec;66(12):7517–7521. doi: 10.1128/jvi.66.12.7517-7521.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Galetto-Lacour A., Yerly S., Perneger T. V., Baumberger C., Hirschel B., Perrin L. Prognostic value of viremia in patients with long-standing human immunodeficiency virus infection. Swiss HIV Cohort Study Group. J Infect Dis. 1996 Jun;173(6):1388–1393. doi: 10.1093/infdis/173.6.1388. [DOI] [PubMed] [Google Scholar]
  9. Heeney J. L., Holterman L., ten Haaft P., Dubbes R., Koornstra W., Teeuwsen V., Bourquin P., Norley S., Niphuis H. Vaccine protection and reduced virus load from heterologous macaque-propagated SIV challenge. AIDS Res Hum Retroviruses. 1994;10 (Suppl 2):S117–S121. [PubMed] [Google Scholar]
  10. Hirsch V. M., Fuerst T. R., Sutter G., Carroll M. W., Yang L. C., Goldstein S., Piatak M., Jr, Elkins W. R., Alvord W. G., Montefiori D. C. Patterns of viral replication correlate with outcome in simian immunodeficiency virus (SIV)-infected macaques: effect of prior immunization with a trivalent SIV vaccine in modified vaccinia virus Ankara. J Virol. 1996 Jun;70(6):3741–3752. doi: 10.1128/jvi.70.6.3741-3752.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoxie J. A., Haggarty B. S., Bonser S. E., Rackowski J. L., Shan H., Kanki P. J. Biological characterization of a simian immunodeficiency virus-like retrovirus (HTLV-IV): evidence for CD4-associated molecules required for infection. J Virol. 1988 Aug;62(8):2557–2568. doi: 10.1128/jvi.62.8.2557-2568.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kestler H., Kodama T., Ringler D., Marthas M., Pedersen N., Lackner A., Regier D., Sehgal P., Daniel M., King N. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science. 1990 Jun 1;248(4959):1109–1112. doi: 10.1126/science.2160735. [DOI] [PubMed] [Google Scholar]
  13. Letvin N. L., Li J., Halloran M., Cranage M. P., Rud E. W., Sodroski J. Prior infection with a nonpathogenic chimeric simian-human immunodeficiency virus does not efficiently protect macaques against challenge with simian immunodeficiency virus. J Virol. 1995 Jul;69(7):4569–4571. doi: 10.1128/jvi.69.7.4569-4571.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lohman B. L., Higgins J., Marthas M. L., Marx P. A., Pedersen N. C. Development of simian immunodeficiency virus isolation, titration, and neutralization assays which use whole blood from rhesus monkeys and an antigen capture enzyme-linked immunosorbent assay. J Clin Microbiol. 1991 Oct;29(10):2187–2192. doi: 10.1128/jcm.29.10.2187-2192.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lohman B. L., McChesney M. B., Miller C. J., McGowan E., Joye S. M., Van Rompay K. K., Reay E., Antipa L., Pedersen N. C., Marthas M. L. A partially attenuated simian immunodeficiency virus induces host immunity that correlates with resistance to pathogenic virus challenge. J Virol. 1994 Nov;68(11):7021–7029. doi: 10.1128/jvi.68.11.7021-7029.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lohman B. L., Miller C. J., McChesney M. B. Antiviral cytotoxic T lymphocytes in vaginal mucosa of simian immunodeficiency virus-infected rhesus macaques. J Immunol. 1995 Dec 15;155(12):5855–5860. [PMC free article] [PubMed] [Google Scholar]
  17. Lu X. S., Bélec L., Pillot J. Anti-gp160 IgG and IgA antibodies associated with a large increase in total IgG in cervicovaginal secretions from human immunodeficiency virus type 1-infected women. J Infect Dis. 1993 May;167(5):1189–1192. doi: 10.1093/infdis/167.5.1189. [DOI] [PubMed] [Google Scholar]
  18. Lu Y., Brosio P., Lafaile M., Li J., Collman R. G., Sodroski J., Miller C. J. Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques. J Virol. 1996 May;70(5):3045–3050. doi: 10.1128/jvi.70.5.3045-3050.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Marthas M. L., Banapour B., Sutjipto S., Siegel M. E., Marx P. A., Gardner M. B., Pedersen N. C., Luciw P. A. Rhesus macaques inoculated with molecularly cloned simian immunodeficiency virus. J Med Primatol. 1989;18(3-4):311–319. [PubMed] [Google Scholar]
  20. Marthas M. L., Miller C. J., Sutjipto S., Higgins J., Torten J., Lohman B. L., Unger R. E., Ramos R. A., Kiyono H., McGhee J. R. Efficacy of live-attenuated and whole-inactivated simian immunodeficiency virus vaccines against vaginal challenge with virulent SIV. J Med Primatol. 1992 Feb-May;21(2-3):99–107. [PubMed] [Google Scholar]
  21. Marthas M. L., Ramos R. A., Lohman B. L., Van Rompay K. K., Unger R. E., Miller C. J., Banapour B., Pedersen N. C., Luciw P. A. Viral determinants of simian immunodeficiency virus (SIV) virulence in rhesus macaques assessed by using attenuated and pathogenic molecular clones of SIVmac. J Virol. 1993 Oct;67(10):6047–6055. doi: 10.1128/jvi.67.10.6047-6055.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Marx P. A., Compans R. W., Gettie A., Staas J. K., Gilley R. M., Mulligan M. J., Yamshchikov G. V., Chen D., Eldridge J. H. Protection against vaginal SIV transmission with microencapsulated vaccine. Science. 1993 May 28;260(5112):1323–1327. doi: 10.1126/science.8493576. [DOI] [PubMed] [Google Scholar]
  23. Mellors J. W., Rinaldo C. R., Jr, Gupta P., White R. M., Todd J. A., Kingsley L. A. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science. 1996 May 24;272(5265):1167–1170. doi: 10.1126/science.272.5265.1167. [DOI] [PubMed] [Google Scholar]
  24. Miller C. J., Alexander N. J., Sutjipto S., Joye S. M., Hendrickx A. G., Jennings M., Marx P. A. Effect of virus dose and nonoxynol-9 on the genital transmission of SIV in rhesus macaques. J Med Primatol. 1990;19(3-4):401–409. [PubMed] [Google Scholar]
  25. Miller C. J., Alexander N. J., Sutjipto S., Lackner A. A., Gettie A., Hendrickx A. G., Lowenstine L. J., Jennings M., Marx P. A. Genital mucosal transmission of simian immunodeficiency virus: animal model for heterosexual transmission of human immunodeficiency virus. J Virol. 1989 Oct;63(10):4277–4284. doi: 10.1128/jvi.63.10.4277-4284.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Miller C. J., Alexander N. J., Vogel P., Anderson J., Marx P. A. Mechanism of genital transmission of SIV: a hypothesis based on transmission studies and the location of SIV in the genital tract of chronically infected female rhesus macaques. J Med Primatol. 1992 Feb-May;21(2-3):64–68. [PubMed] [Google Scholar]
  27. Miller C. J., Kang D. W., Marthas M., Moldoveanu Z., Kiyono H., Marx P., Eldridge J. H., Mestecky J., McGhee J. R. Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques. Clin Exp Immunol. 1992 Jun;88(3):520–526. doi: 10.1111/j.1365-2249.1992.tb06481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miller C. J., Marthas M., Torten J., Alexander N. J., Moore J. P., Doncel G. F., Hendrickx A. G. Intravaginal inoculation of rhesus macaques with cell-free simian immunodeficiency virus results in persistent or transient viremia. J Virol. 1994 Oct;68(10):6391–6400. doi: 10.1128/jvi.68.10.6391-6400.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Miller C. J., McGhee J. R., Gardner M. B. Mucosal immunity, HIV transmission, and AIDS. Lab Invest. 1993 Feb;68(2):129–145. [PubMed] [Google Scholar]
  30. Miller C. J. Mucosal transmission of simian immunodeficiency virus. Curr Top Microbiol Immunol. 1994;188:107–122. doi: 10.1007/978-3-642-78536-8_6. [DOI] [PubMed] [Google Scholar]
  31. Miller C. J., Vogel P., Alexander N. J., Sutjipto S., Hendrickx A. G., Marx P. A. Localization of SIV in the genital tract of chronically infected female rhesus macaques. Am J Pathol. 1992 Sep;141(3):655–660. [PMC free article] [PubMed] [Google Scholar]
  32. Miller C., Gardner M. B. AIDS and mucosal immunity: usefulness of the SIV macaque model of genital mucosal transmission. J Acquir Immune Defic Syndr. 1991;4(12):1169–1172. [PubMed] [Google Scholar]
  33. Moore J. P., Cao Y., Leu J., Qin L., Korber B., Ho D. D. Inter- and intraclade neutralization of human immunodeficiency virus type 1: genetic clades do not correspond to neutralization serotypes but partially correspond to gp120 antigenic serotypes. J Virol. 1996 Jan;70(1):427–444. doi: 10.1128/jvi.70.1.427-444.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. O'Brien T. R., Blattner W. A., Waters D., Eyster E., Hilgartner M. W., Cohen A. R., Luban N., Hatzakis A., Aledort L. M., Rosenberg P. S. Serum HIV-1 RNA levels and time to development of AIDS in the Multicenter Hemophilia Cohort Study. JAMA. 1996 Jul 10;276(2):105–110. [PubMed] [Google Scholar]
  35. Pachl C., Todd J. A., Kern D. G., Sheridan P. J., Fong S. J., Stempien M., Hoo B., Besemer D., Yeghiazarian T., Irvine B. Rapid and precise quantification of HIV-1 RNA in plasma using a branched DNA signal amplification assay. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Apr 15;8(5):446–454. doi: 10.1097/00042560-199504120-00003. [DOI] [PubMed] [Google Scholar]
  36. Putkonen P., Walther L., Zhang Y. J., Li S. L., Nilsson C., Albert J., Biberfeld P., Thorstensson R., Biberfeld G. Long-term protection against SIV-induced disease in macaques vaccinated with a live attenuated HIV-2 vaccine. Nat Med. 1995 Sep;1(9):914–918. doi: 10.1038/nm0995-914. [DOI] [PubMed] [Google Scholar]
  37. Sutjipto S., Pedersen N. C., Miller C. J., Gardner M. B., Hanson C. V., Gettie A., Jennings M., Higgins J., Marx P. A. Inactivated simian immunodeficiency virus vaccine failed to protect rhesus macaques from intravenous or genital mucosal infection but delayed disease in intravenously exposed animals. J Virol. 1990 May;64(5):2290–2297. doi: 10.1128/jvi.64.5.2290-2297.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Travers K., Mboup S., Marlink R., Guèye-Nidaye A., Siby T., Thior I., Traore I., Dieng-Sarr A., Sankalé J. L., Mullins C. Natural protection against HIV-1 infection provided by HIV-2. Science. 1995 Jun 16;268(5217):1612–1615. doi: 10.1126/science.7539936. [DOI] [PubMed] [Google Scholar]
  39. Unger R. E., Marthas M. L., Lackner A. A., Pratt-Lowe E., Lohman B. L., Van Rompay K., Luciw P. A. Detection of simian immunodeficiency virus DNA in macrophages from infected rhesus macaques. J Med Primatol. 1992 Feb-May;21(2-3):74–81. [PubMed] [Google Scholar]
  40. Wigzell H. Prospects for an HIV-vaccine. FASEB J. 1991 Jul;5(10):2406–2411. doi: 10.1096/fasebj.5.10.2065889. [DOI] [PubMed] [Google Scholar]
  41. Wyand M. S., Manson K. H., Garcia-Moll M., Montefiori D., Desrosiers R. C. Vaccine protection by a triple deletion mutant of simian immunodeficiency virus. J Virol. 1996 Jun;70(6):3724–3733. doi: 10.1128/jvi.70.6.3724-3733.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]

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