Bonsignori Mattia, Liao Hua-Xin, Gao Feng, Williams Wilton B, Alam S Munir, Montefiori David C, Haynes Barton F
Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC, USA.
Immunol Rev. 2017 Jan;275(1):145-160. doi: 10.1111/imr.12509.
Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the viral and immunologic events that occur during HIV-1 infection, and then to mimic those events with a vaccine formulation. This concept has led to efforts to map both virus and antibody events that occur from the time of HIV-1 transmission to development of bnAbs. This work has revealed that a virus-antibody "arms race" occurs in which a HIV-1 transmitted/founder (TF) Env induces autologous neutralizing antibodies that can not only neutralize the TF virus but also can select virus escape mutants that in turn select affinity-matured neutralizing antibodies. From these studies has come a picture of bnAb development that has led to new insights in host-pathogen interactions and, as well, led to insight into immunologic mechanisms of control of bnAb development. Here, we review the progress to date in elucidating bnAb B cell lineages in HIV-1 infection, discuss new research leading to understanding the immunologic mechanisms of bnAb induction, and address issues relevant to the use of this information for the design of new HIV-1 sequential envelope vaccine candidates.
迄今为止，仅在HIV-1感染的情况下观察到诱导HIV-1广泛中和抗体（bnAbs），而且是在HIV传播数年之后才出现。因此，出现了这样一种概念，即诱导bnAbs的一条途径是确定HIV-1感染期间发生的病毒和免疫事件，然后用疫苗制剂模拟这些事件。这一概念促使人们努力绘制从HIV-1传播到bnAbs产生过程中发生的病毒和抗体事件。这项工作揭示了一种病毒-抗体“军备竞赛”的发生，其中HIV-1传播/奠基者（TF）Env诱导自体中和抗体，这些抗体不仅可以中和TF病毒，还可以选择病毒逃逸突变体，而这些突变体又会选择亲和力成熟的中和抗体。从这些研究中得出了bnAb产生的图景，这不仅为宿主-病原体相互作用带来了新的见解，也为bnAb产生的免疫控制机制提供了见解。在这里，我们回顾了迄今为止在阐明HIV-1感染中bnAb B细胞谱系方面取得的进展，讨论了导致理解bnAb诱导免疫机制的新研究，并探讨了将这些信息用于设计新型HIV-1序贯包膜疫苗候选物的相关问题。
