原文出處：

Science Translational Medicine DOI： 10.1126/scitranslmed.3002351

Letvin, Norman L.; Rao, Srinivas S.; Montefiori, David C.; Seaman, Michael S.; Sun, Yue; Lim, So-Yon; Yeh, Wendy W.; Asmal, Mohammed; Gelman, Rebecca S.; Shen, Ling; Whitney, James B.; Seoighe, Cathal; Lacerda, Miguel; Keating, Sheila; Norris, Philip J.; Hudgens, Michael G.; Gilbert, Peter B.; Buzby, Adam P.; Mach, Linh V.; Zhang, Jinrong; Balachandran, Harikrishnan; Shaw, George M.; Schmidt, Stephen D.; Todd, John-Paul; Dodson, Alan; Mascola, John R.; Nabel, Gary J.

The RV144 vaccine trial in Thailand demonstrated that an HIV vaccine could prevent infection in humans and highlights theimportance of understanding protective immunity against HIV. We used a nonhuman primate model to define immune and geneticmechanisms of protection against mucosal infection by the simian immunodeficiency virus （SIV）. A plasmid DNA prime/recombinantadenovirus serotype 5 （rAd5） boost vaccine regimen was evaluated for its ability to protect monkeys from infection by SIVmac251or SIVsmE660 isolates after repeat intrarectal challenges. Although this prime-boost vaccine regimen failed to protect againstSIVmac251 infection, 50% of vaccinated monkeys were protected from infection with SIVsmE660. Among SIVsmE660-infected animals,there was about a one-log reduction in peak plasma virus RNA in monkeys expressing the major histocompatibility complex classI allele Mamu-A*01, implicating cytotoxic T lymphocytes in the control of SIV replication once infection is established. Among Mamu-A*01–negative monkeys challenged with SIVsmE660, no CD8+ T cell response or innate immune response was associated with protection against virus acquisition. However, low levels ofneutralizing antibodies and an envelope-specific CD4+ T cell response were associated with vaccine protection in these monkeys. Moreover, monkeys that expressed two TRIM5 alleles that restrict SIV replication were more likely to be protected from infection than monkeys that expressed at leastone permissive TRIM5 allele. This study begins to elucidate the mechanisms of vaccine protection against immunodeficiency viruses and highlightsthe need to analyze these immune and genetic correlates of protection in future trials of HIV vaccine strategies.