Noto Alessandra, Pantaleo Giuseppe
aService of Immunology and Allergy bSwiss Vaccine Research Institute, Lausanne University Hospital, Lausanne, Switzerland.
Curr Opin HIV AIDS. 2017 May;12(3):203-208. doi: 10.1097/COH.0000000000000359.
The purpose of the present review is to provide an update on the current development in the field of broadly neutralizing antibodies (bNabs) and their potential use in the prevention and therapeutic settings, and an evaluation of the B-cell abnormalities that may impair antibody responses in HIV infection.
Major advances have been achieved in the characterization of bNabs directed against different vulnerable regions of HIV Envelope (Env). Recent observations have clearly demonstrated the ability of bNabs to prevent HIV infection in the nonhuman primate model of HIV infection and to suppress viremia in individuals with chronic HIV infection in the absence of antiretroviral therapy. Furthermore, substantial advances have also been obtained in the development of HIV Env proteins and immunization strategies inducing bNabs in small animal models. Several studies have also shed light on the B-cell abnormalities associated with the viremic phase of HIV infection that cause impaired B-cell maturation and antibody responses. Of note, preliminary observations have provided evidence for a correlation between the expansion of a specific population of B cells, for example, germinal center B cells, the expansion of T follicular helper cells (Tfh), and the generation of neutralizing antibodies.
The recent observations on the antiviral effects of bNabs in vivo indicate that bNabs may play a central role in both the prevention and the therapeutic settings. The identification of the role of germinal center B cells and Tfh cells as critical components of the immune response leading to the generation of neutralizing antibodies, will allow the development of specific immunization strategies for the stimulation of germinal center B cells and Tfh cells. A lot of work still remains to be done for the delineation of B-cell and Tfh cell biology from human lymphoid tissues and in the development of HIV Env proteins and immunization strategies leading to the generation of bNabs.
本综述旨在提供关于广泛中和抗体（bNabs）领域当前进展及其在预防和治疗方面潜在应用的最新信息，并评估可能损害HIV感染中抗体反应的B细胞异常情况。
在针对HIV包膜（Env）不同易感区域的bNabs特性研究方面取得了重大进展。近期观察结果清楚地表明，bNabs能够在HIV感染的非人灵长类动物模型中预防HIV感染，并在无抗逆转录病毒治疗的情况下抑制慢性HIV感染个体的病毒血症。此外，在HIV Env蛋白开发以及在小动物模型中诱导bNabs的免疫策略方面也取得了实质性进展。多项研究还揭示了与HIV感染病毒血症期相关的B细胞异常情况，这些异常会导致B细胞成熟和抗体反应受损。值得注意的是，初步观察结果为特定B细胞群体（如生发中心B细胞）的扩增、滤泡辅助性T细胞（Tfh）的扩增与中和抗体产生之间的相关性提供了证据。
近期关于bNabs体内抗病毒作用的观察表明，bNabs可能在预防和治疗方面都发挥核心作用。确定生发中心B细胞和Tfh细胞作为导致中和抗体产生的免疫反应关键组成部分的作用，将有助于开发刺激生发中心B细胞和Tfh细胞的特定免疫策略。在从人类淋巴组织中描绘B细胞和Tfh细胞生物学特性以及开发导致产生bNabs的HIV Env蛋白和免疫策略方面，仍有许多工作要做。
