期刊
JOURNAL OF VIROLOGY
卷 92, 期 16, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00690-18
关键词
AIDS; human immunodeficiency virus; simian immunodeficiency virus; vaccines
类别
资金
- Public Health Service (PHS) from the National Institute of Allergy and Infectious Diseases [R56 AI049120, R37 AI052056, P01 AI104715]
- PHS grant [R01 AI121135]
- Office of Research Infrastructure Programs [P51 OD011106]
- National Cancer Institute, National Institutes of Health [HHSN261200800001E]
- Bill & Melinda Gates Foundation
- Ministry of Foreign Affairs of Denmark
- Irish Aid
- Ministry of Finance of Japan
- Ministry of Foreign Affairs of the Netherlands
- Norwegian Agency for Development Cooperation (NORAD)
- United Kingdom Department for International Development (DFID)
- United States Agency for International Development (USAID)
Certain major histocompatibility complex class I (MHC-I) alleles are associated with spontaneous control of viral replication in human immunodeficiency virus (HIV)-infected people and simian immunodeficiency virus (SIV)infected rhesus macaques (RMs). These cases of elite control of HIV/SIV replication are often immune-mediated, thereby providing a framework for studying anti-lentiviral immunity. In this study, we examined how vaccination impacts SIV replication in RMs expressing the MHC-I allele Mamu-B*17. Approximately 21% of Mamu-B*17(+) and 50% of Mamu-B*08(+) RMs control chronic-phase viremia after SIVmac239 infection. Because CD8(+) T cells targeting Mamu-B*08-restricted SIV epitopes have been implicated in virologic suppression in Mamu-B*08(+) RMs, we investigated whether this might also be true for Mamu-B*17(+) RMs. Two groups of Mamu-B*17(+) RMs were vaccinated with genes encoding Mamu-B*17-restricted epitopes in Vif and Nef. These genes were delivered by themselves (group 1) or together with env (group 2). Group 3 included MHC-I-matched RMs and served as the control group. Surprisingly, the group 1 vaccine regimen had little effect on viral replication compared to group 3, suggesting that unlike Mamu-B*08(+) RMs, preexisting SIV-specific CD8(+) T cells alone do not facilitate long-term virologic suppression in Mamu-B*17(+) RMs. Remarkably, however, 5/8 group 2 vaccinees controlled viremia to <15 viral RNA copies/ml soon after infection. No serological neutralizing activity against SIVmac239 was detected in group 2, although vaccine-elicited gp140-binding antibodies correlated inversely with nadir viral loads. Collectively, these data shed new light on the unique mechanism of elite control in Mamu-B*17(+) RMs and implicate vaccine-induced, nonneutralizing antiEnv anti-bodies in the containment of immunodeficiency virus infection. IMPORTANCE A better understanding of the immune correlates of protection against HIV might facilitate the development of a prophylactic vaccine. Therefore, we investigated simian immunodeficiency virus (SIV) infection outcomes in rhesus macaques expressing the major histocompatibility complex class I allele Mamu-B*17. Approximately 21% of Mamu-B*17(+) macaques spontaneously controlled chronic phase viremia after SIV infection, an effect that may involve CD8(+) T cells targeting Mamu-B*17-restricted SIV epitopes. We vaccinated Mamu-B*17(+) macaques with genes encoding immunodominant epitopes in Vif and Nef alone (group 1) or together with env (group 2). Although neither vaccine regimen prevented SIV infection, 5/8 group 2 vaccinees controlled viremia to below detection limits shortly after infection. This outcome, which was not observed in group 1, was associated with vaccine-induced, nonneutralizing Env-binding antibodies. Together, these findings suggest a limited contribution of Vif-and Nefspecific CD8(+) T cells for virologic control in Mamu-B*17(+) macaques and implicate antiEnv antibodies in containment of SIV infection.
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