Institute of Medical Virology, University of Zurich, Zurich, Switzerland.
Department of Mathematics, Iowa State University, Ames, Iowa, USA.
Curr Opin HIV AIDS. 2019 Jul;14(4):279-285. doi: 10.1097/COH.0000000000000552.
Broadly neutralizing antibodies (bnAbs) are considered a key component of an effective HIV-1 vaccine, but despite intensive efforts, induction of bnAbs by vaccination has thus far not been possible. Potent bnAb activity is rare in natural infection and a deeper understanding of factors that promote or limit bnAb evolution is critical to guide bnAb vaccine development. This review reflects on recent key discoveries on correlates of bnAb development and discusses what further insights are needed to move forward.
An increasing number of parameters have been implicated to influence bnAb development in natural infection. Most recent findings highlight a range of immune factors linked with bnAb evolution. Novel approaches have brought exciting progress in defining signatures of the viral envelope associated with bnAb activity.
Focused efforts of recent years have unraveled a multiply layered process of HIV-1 bnAb development. As it is understood today, bnAb evolution can be triggered and influenced by a range of factors and several different pathways may exist how bnAb induction and maturation can occur. To capitalize on the gained knowledge, future research needs to validate factors to identify independent drivers of bnAb induction to advance vaccine design.
目的综述：广泛中和抗体（bnAbs）被认为是有效 HIV-1 疫苗的关键组成部分，但尽管进行了深入研究，接种疫苗诱导 bnAbs 至今仍未成功。在自然感染中，强效 bnAb 活性较为罕见，深入了解促进或限制 bnAb 进化的因素对于指导 bnAb 疫苗的开发至关重要。本文回顾了近期关于 bnAb 发展相关因素的重要发现，并讨论了进一步推进研究所需的见解。
最新发现：越来越多的参数被认为会影响自然感染中 bnAb 的发展。最近的研究结果强调了一系列与 bnAb 进化相关的免疫因素。新方法在定义与 bnAb 活性相关的包膜病毒特征方面取得了令人兴奋的进展。
总结：近年来的集中研究揭示了 HIV-1 bnAb 发展的一个多层次过程。就目前的理解而言，bnAb 进化可以被多种因素触发和影响，并且可能存在几种不同的途径，从而可以诱导和成熟 bnAb。为了利用所获得的知识，未来的研究需要验证这些因素，以确定 bnAb 诱导的独立驱动因素，从而推进疫苗的设计。
