Vaccine Research Center, NIAID, NIH, Bethesda, Maryland 20892, USA.
SAIC-Frederick, Frederick National Laboratory, NIH, Frederick, Maryland 21702, USA.
Nature. 2014 Jan 23;505(7484):502-8. doi: 10.1038/nature12893. Epub 2013 Dec 18.
A major challenge for the development of a highly effective AIDS vaccine is the identification of mechanisms of protective immunity. To address this question, we used a nonhuman primate challenge model with simian immunodeficiency virus (SIV). We show that antibodies to the SIV envelope are necessary and sufficient to prevent infection. Moreover, sequencing of viruses from breakthrough infections revealed selective pressure against neutralization-sensitive viruses; we identified a two-amino-acid signature that alters antigenicity and confers neutralization resistance. A similar signature confers resistance of human immunodeficiency virus (HIV)-1 to neutralization by monoclonal antibodies against variable regions 1 and 2 (V1V2), suggesting that SIV and HIV share a fundamental mechanism of immune escape from vaccine-elicited or naturally elicited antibodies. These analyses provide insight into the limited efficacy seen in HIV vaccine trials.
开发高效艾滋病疫苗的主要挑战是确定保护性免疫的机制。为了解决这个问题，我们使用了一种带有猴免疫缺陷病毒（SIV）的非人类灵长类动物挑战模型。我们表明，针对 SIV 包膜的抗体是预防感染所必需且充分的。此外，对突破性感染病毒的测序揭示了对中和敏感病毒的选择压力；我们确定了一个改变抗原性并赋予中和抗性的两个氨基酸特征。类似的特征赋予了人类免疫缺陷病毒（HIV）对针对可变区 1 和 2（V1V2）的单克隆抗体的中和抗性，这表明 SIV 和 HIV 共享一种从疫苗诱导或自然诱导的抗体中逃脱免疫的基本机制。这些分析为 HIV 疫苗试验中观察到的有限疗效提供了深入了解。
