TY - JOUR
T1 - Mamu-B*17+ rhesus macaques vaccinated with env, vif, and nef manifest early control of SIVmac239 replication
AU - Martins, Mauricio A.
AU - Tully, Damien C.
AU - Pedreño-Lopez, Núria
AU - Bredow, Benjamin von
AU - Pauthner, Matthias G.
AU - Shin, Young C.
AU - Yuan, Maoli
AU - Lima, Noemia S.
AU - Bean, David J.
AU - Gonzalez-Nieto, Lucas
AU - Domingues, Aline
AU - Gutman, Martin J.
AU - Maxwell, Helen S.
AU - Magnani, Diogo M.
AU - Ricciardi, Michael J.
AU - Bailey, Varian K.
AU - Altman, John D.
AU - Burton, Dennis R.
AU - Ejima, Keisuke
AU - Allison, David B.
AU - Evans, David T.
AU - Rakasz, Eva G.
AU - Parks, Christopher L.
AU - Bonaldo, Myrna C.
AU - Capuano, Saverio
AU - Lifson, Jeffrey D.
AU - Desrosiers, Ronald C.
AU - Allen, Todd M.
AU - Watkins, David I.
N1 - Publisher Copyright:
© 2018 American Society for Microbiology.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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 anti- Env antibodies in the containment of immunodeficiency virus infection.
AB - 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 anti- Env antibodies in the containment of immunodeficiency virus infection.
KW - AIDS
KW - Human immunodeficiency virus
KW - Simian immunodeficiency virus
KW - Vaccines
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U2 - 10.1128/JVI.00690-18
DO - 10.1128/JVI.00690-18
M3 - Article
C2 - 29875239
AN - SCOPUS:85050821251
VL - 92
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 16
M1 - e00690-18
ER -