美国斯克利普斯研究所
研究人员在一项随机、双盲、安慰剂对照的1期临床试验中发现，HIV疫苗引物候选者eOD-GT8 60mer与AS01B佐剂具有良好的安全性，并在97%的疫苗接受者中诱导出VRC01级广义中和抗体（bnAb）前体，血液中免疫球蛋白G B细胞的中位频率达到0.1%。bnAb前体与bnAb共享特性，并在提升中获得体细胞超敏变和亲和力。这些结果确立了生殖细胞靶向疫苗活化的临床概念证明，支持开发诱导bnAb的增强方案，并鼓励将生殖细胞靶向策略应用于艾滋病毒和其他病原体的其他靶标。
据介绍，bnAb可以保护人们免受HIV感染，但还没有通过人类疫苗接种诱导出来。诱导bnAb的一个关键障碍是对罕见的bnAb前体B细胞进行疫苗诱导。
附：英文原文
Title: Vaccination induces HIV broadly neutralizing antibody precursors in humans
Author: David J. Leggat, Kristen W. Cohen, Jordan R. Willis, William J. Fulp, Allan C. deCamp, Oleksandr Kalyuzhniy, Christopher A. Cottrell, Sergey Menis, Greg Finak, Lamar Ballweber-Fleming, Abhinaya Srikanth, Jason R. Plyler, Torben Schiffner, Alessia Liguori, Farhad Rahaman, Angela Lombardo, Vincent Philiponis, Rachael E. Whaley, Aaron Seese, Joshua Brand, Alexis M. Ruppel, Wesley Hoyland, Nicole L. Yates, LaTonya D. Williams, Kelli Greene, Hongmei Gao, Celia R. Mahoney, Martin M. Corcoran, Alberto Cagigi, Alison Taylor, David M. Brown, David R. Ambrozak, Troy Sincomb, Xiaozhen Hu, Ryan Tingle, Erik Georgeson, Saman Eskandarzadeh, Nushin Alavi, Danny Lu, Tina-Marie Mullen, Michael Kubitz, Bettina Groschel, Janine Maenza, Orpheus Kolokythas, Nadia Khati, Jeffrey Bethony, Shane Crotty, Mario Roederer, Gunilla B. Karlsson Hedestam, Georgia D. Tomaras, David Montefiori, David Diemert, Richard A. Koup, Dagna S. Laufer, M. Juliana McElrath, Adrian B. McDermott, William R. Schief
Issue&Volume: 2022-12-02
Abstract: Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine–priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.
DOI: add6502
Source: https://www.science.org/doi/10.1126/science.add6502