美国杜克大学Barton F. Haynes等研究人员合作实现人类异源HIV-1中和抗体B细胞谱系的疫苗诱导。该项研究成果于2024年5月17日在线发表在《细胞》杂志上。
研究人员表示，HIV疫苗开发的一个关键障碍是无法在人类体内诱导出B细胞谱系的广泛中和抗体（bnAb）。在HIV-1感染者中，bnAb需要数年才能形成。HVTN 133临床试验研究了一种针对B细胞谱系的HIV-1包膜（Env）膜近端外部区域（MPER）bnAb的肽/脂质体免疫原（NCT03934541）。
研究人员报告了MPER多肽脂质体诱导成熟bnAb及其前体的多克隆HIV-1 B细胞谱系，其中最有效的bnAb能中和15%的全球2级HIV-1毒株和35%的B族毒株，并在第二次免疫后启动了B细胞谱系。疫苗选择了不可能发生的突变，增加了抗体与gp41和脂质的结合，从而增强了中和效果。这项研究证明了，快速疫苗诱导具有异源中和活性的人类B细胞谱系和选择抗体不可能突变的概念，并为成功开发HIV-1疫苗勾勒出了一条道路。
附：英文原文
Title: Vaccine induction of heterologous HIV-1-neutralizing antibody B cell lineages in humans
Author: Wilton B. Williams, S. Munir Alam, Gilad Ofek, Nathaniel Erdmann, David C. Montefiori, Michael S. Seaman, Kshitij Wagh, Bette Korber, Robert J. Edwards, Katayoun Mansouri, Amanda Eaton, Derek W. Cain, Mitchell Martin, JongIn Hwang, Aria Arus-Altuz, Xiaozhi Lu, Fangping Cai, Nolan Jamieson, Robert Parks, Maggie Barr, Andrew Foulger, Kara Anasti, Parth Patel, Salam Sammour, Ruth J. Parsons, Xiao Huang, Jared Lindenberger, Susan Fetics, Katarzyna Janowska, Aurelie Niyongabo, Benjamin M. Janus, Anagh Astavans, Christopher B. Fox, Ipsita Mohanty, Tyler Evangelous, Yue Chen, Madison Berry, Helene Kirshner, Elizabeth Van Itallie, Kevin O. Saunders, Kevin Wiehe, Kristen W. Cohen, M. Juliana McElrath, Lawrence Corey, Priyamvada Acharya, Stephen R. Walsh, Lindsey R. Baden, Barton F. Haynes
Issue&Volume: 2024-05-17
Abstract: A critical roadblock to HIV vaccine development is the inability to induce B cell lineages of broadly neutralizing antibodies (bnAbs) in humans. In people living with HIV-1, bnAbs take years to develop. The HVTN 133 clinical trial studied a peptide/liposome immunogen targeting B cell lineages of HIV-1 envelope (Env) membrane-proximal external region (MPER) bnAbs (NCT03934541). Here, we report MPER peptide-liposome induction of polyclonal HIV-1 B cell lineages of mature bnAbs and their precursors, the most potent of which neutralized 15% of global tier 2 HIV-1 strains and 35% of clade B strains with lineage initiation after the second immunization. Neutralization was enhanced by vaccine selection of improbable mutations that increased antibody binding to gp41 and lipids. This study demonstrates proof of concept for rapid vaccine induction of human B cell lineages with heterologous neutralizing activity and selection of antibody improbable mutations and outlines a path for successful HIV-1 vaccine development.
DOI: 10.1016/j.cell.2024.04.033
Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00459-8