美国杜克大学Barton F. Haynes等研究人员合作实现猕猴体内CD4模拟HIV-1广泛中和抗体前体的疫苗诱导。这一研究成果于2024年1月4日发表在国际学术期刊《细胞》上。
研究人员表示，CD4结合位点（CD4bs）是HIV-1包膜（Env）上的一个保守表位，可被保护性广谱中和抗体（bnAbs）靶向。由于多种原因，包括CD4bs被聚糖阻塞、免疫原扩增了适当的初始B细胞以及功能性抗体突变的选择，HIV-1疫苗未能激发CD4bs bnAbs。
研究人员证明了用CD4bs靶向免疫原免疫猕猴会诱导出具有CD4模仿bnAbs结构和遗传特征的中和bnAb前体。与HIV-1 Env结合的CD4bs nAb结构显示了所有已知人类CD4模仿bnAb的结合角和重链相互作用特征。猕猴nAb来自与人类VH1-46级bnAb基因同源的可变和连接基因片段。这项疫苗研究启动了灵长类动物的B细胞，CD4bs bnAb可从B细胞中衍生出来，并完成了开发有效HIV-1疫苗的关键第一步。
附：英文原文
Title: Vaccine induction of CD4-mimicking HIV-1 broadly neutralizing antibody precursors in macaques
Author: Kevin O. Saunders, James Counts, Bhishem Thakur, Victoria Stalls, Robert Edwards, Kartik Manne, Xiaozhi Lu, Katayoun Mansouri, Yue Chen, Rob Parks, Maggie Barr, Laura Sutherland, Joena Bal, Nicholas Havill, Haiyan Chen, Emily Machiele, Nolan Jamieson, Bhavna Hora, Megan Kopp, Katarzyna Janowska, Kara Anasti, Chuancang Jiang, Elizabeth Van Itallie, Sravani Venkatayogi, Amanda Eaton, Rory Henderson, Christopher Barbosa, S. Munir Alam, Sampa Santra, Drew Weissman, M. Anthony Moody, Derek W. Cain, Ying K. Tam, Mark Lewis, Wilton B. Williams, Kevin Wiehe, David C. Montefiori, Priyamvada Acharya, Barton F. Haynes
Issue&Volume: 2024/01/04
Abstract: The CD4-binding site (CD4bs) is a conserved epitope on HIV-1 envelope (Env) that canbe targeted by protective broadly neutralizing antibodies (bnAbs). HIV-1 vaccineshave not elicited CD4bs bnAbs for many reasons, including the occlusion of CD4bs byglycans, expansion of appropriate naive B cells with immunogens, and selection offunctional antibody mutations. Here, we demonstrate that immunization of macaqueswith a CD4bs-targeting immunogen elicits neutralizing bnAb precursors with structuraland genetic features of CD4-mimicking bnAbs. Structures of the CD4bs nAb bound toHIV-1 Env demonstrated binding angles and heavy-chain interactions characteristicof all known human CD4-mimicking bnAbs. Macaque nAb were derived from variable andjoining gene segments orthologous to the genes of human VH1-46-class bnAb. This vaccinestudy initiated in primates the B cells from which CD4bs bnAbs can derive, accomplishingthe key first step in the development of an effective HIV-1 vaccine.
DOI: 10.1016/j.cell.2023.12.002
Source: https://www.cell.com/cell/fulltext/S0092-8674(23)01334-X