Nature2014-06-26 4:43 PM

HIV/AIDS疫苗存在的问题 Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV

论文摘要 

“人免疫缺陷病毒-1”(HIV-1)疫苗的临床试验迄今为止是令人失望的,不是疗效低就是没疗效(零保护)。在这篇论文中,Mario Roederer等人分析了多疫苗方案在“猴免疫缺陷病毒”(SIV)的恒河猴模型中的效果,发现了一个关键的“二氨基酸”特征,它使病毒对中和抗体产生抵抗力。免疫逃避的一个类似机制被发现在HIV中也起作用,说明这种类型的由疫苗引发的抗体反应也许可解释为什么在HIV疫苗试验中疗效有限。

Abstract 

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.

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