Humoral Immunology Unit, Institut Pasteur, Université Paris Cité, INSERM U1222, Paris 75015, France.
NanoImaging Core Facility, Centre de Ressources et Recherches Technologiques (C2RT), Université Paris Cité, Institut Pasteur, Paris 75015, France.
Cell Host Microbe. 2023 Aug 9;31(8):1275-1287.e8. doi: 10.1016/j.chom.2023.06.006. Epub 2023 Jul 10.
HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the GDIR V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies.
HIV-1 广谱中和抗体（bNAbs）可以降低病毒载量，但通常无法抵抗逃避抗体压力的自体病毒。尽管如此，bNAbs 可能有助于接受抗逆转录病毒治疗（ART）的个体自然控制 HIV-1。在这里，我们描述了在治疗后控制者（PTC）中诱导的 bNAb B 细胞谱系，该谱系表现出广泛的血清中和作用，并表明该谱系中的代表性抗体 EPTC112 针对 HIV-1 包膜糖蛋白糖基化-V3 环超位点的四级表位。与可溶性 BG505 SOSIP.664 包膜三聚体复合的 EPTC112 的冷冻电镜结构显示与 N301-和 N156-支化 N-聚糖以及 GDIR V3 环基序相互作用。尽管该 PTC 中唯一同时循环的病毒对 EPTC112 具有抗性，但它被该个体的自身血浆 IgG 抗体强烈中和。我们的研究结果阐明了交叉中和抗体如何改变 PTC 中的 HIV-1 感染过程，并可能控制 ART 外的病毒血症，支持它们在功能性 HIV-1 治愈策略中的作用。
