Ragon Institute of MGH, MIT and Harvard, Cambridge, Massachusetts 02139-3583; email:
Annu Rev Med. 2016;67:185-200. doi: 10.1146/annurev-med-091014-090749. Epub 2015 Nov 9.
HIV-1 poses immense immunological challenges to the humoral immune response because of its ability to shield itself and replicate and evolve rapidly. Although most currently licensed vaccines provide protection via the induction of antibodies (Abs) that can directly block infection ( 1 ), 30 years of HIV-1 vaccine research has failed to successfully elicit such Abs against globally relevant HIV strains. However, mounting evidence suggests that these broadly neutralizing antibodies (bNAbs) do emerge naturally in a significant fraction of infected subjects, albeit after years of infection, indicating that these responses can be selected naturally by the immune response but take long periods of time to evolve. We review the basic structural characteristics of broadly neutralizing antibodies and how they recognize the virus, and we discuss new vaccination strategies that aim to mimic natural evolution to guide B cells to produce protective Abs against HIV-1.
HIV-1 对体液免疫反应构成了巨大的免疫挑战，因为它能够自我保护、快速复制和进化。尽管大多数目前获得许可的疫苗通过诱导能够直接阻断感染的抗体 (Abs) 来提供保护 (1)，但 30 年来的 HIV-1 疫苗研究未能成功地针对全球相关的 HIV 株诱导出这种 Abs。然而，越来越多的证据表明，这些广泛中和抗体 (bNAbs) 确实会在很大一部分感染的受试者中自然出现，尽管是在感染多年后才出现，这表明这些反应可以被免疫反应自然选择，但需要很长时间才能进化。我们回顾了广泛中和抗体的基本结构特征及其识别病毒的方式，并讨论了旨在模仿自然进化以指导 B 细胞产生针对 HIV-1 的保护性 Abs 的新疫苗接种策略。
