原文出處：
Science Translational Medicine DOI： 10.1126/scitranslmed.3002351
Immune and Genetic Correlates of Vaccine Protection Against Mucosal Infection by SIV in Monkeys
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.
一項新的研究報告說，猴子中的某些免疫和遺傳學特征可增加某種猴類免疫缺陷病毒（或稱SIV）疫苗的有效性。由于SIV與人類免疫缺陷性病毒（或稱）有著密切的關系，這些發現支持這樣的觀念，即某些人可能帶有某些基因或免疫系統的特征，使得他們能夠比其他人更好地抵御。相關論文發表于《科學—轉化醫學》。
在創制一種有效的疫苗的道路上所遭遇的一個主要障礙是，人們對某個特別的疫苗所產生的有益的免疫反應缺乏了解。迄今為止，在疫苗的試驗中*顯示出具有保護性效應的是在2003年至2006年間在泰國開展的RV144試驗。
這里，Norman Letvin及其同事立志搞清楚類似的SIV疫苗究竟是如何阻止感染的。研究人員給一大群的恒河猴接種了SIV疫苗，接著在一個為其2個星期的時間段中，研究人員反復地給這些猴子注射低劑量的SIV。有一半的猴子產生了對SIV的抵御力，而另外一半的猴子則受到病毒的感染。
接下來，該研究團隊在受到保護的猴子中觀察了3個層面的免疫反應：細胞免疫反應、先天免疫反應以及抗體反應。這些猴子的細胞免疫反應和先天免疫反應沒有受到疫苗的足夠刺激以提供機體保護，但研究人員卻在它們的抗體反應有引人注目發現。低濃度的中和抗體與抵御SIV能力的增加之間具有關聯性。在受到疫苗保護的猴子體內的中和抗體能夠與病毒結合并阻斷其感染細胞的能力。
研究人員還發現了一種保護性的遺傳預測因子：一種叫做TRIM5的基因。那些機體表達某種形式的TRIM5的猴子能夠比沒有該基因的猴子更好地抵抗病毒感染。這兩種特質本身都能提供機體保護效應，但兼具基因和免疫特質的猴子能夠得到疫苗的*保護。
這些結果凸顯了在將來參加疫苗試驗的志愿者中仔細察看這些免疫和基因特質類型的必要性。
