Article
作者: Diemert, David ; Gao, Hongmei ; Taylor, Alison ; Hoyland, Wesley ; Cohen, Kristen W. ; Srikanth, Abhinaya ; Plyler, Jason R. ; Schiffner, Torben ; Ruppel, Alexis M. ; Cagigi, Alberto ; Kolokythas, Orpheus ; Sincomb, Troy ; Crotty, Shane ; Seese, Aaron ; Tingle, Ryan ; Lu, Danny ; Philiponis, Vincent ; Schief, William R. ; Montefiori, David ; Koup, Richard A. ; Yates, Nicole L. ; Cottrell, Christopher A. ; Brand, Joshua ; Khati, Nadia ; Hu, Xiaozhen ; Kubitz, Michael ; Rahaman, Farhad ; Kalyuzhniy, Oleksandr ; Ambrozak, David R. ; Liguori, Alessia ; Whaley, Rachael E. ; deCamp, Allan C. ; Finak, Greg ; Willis, Jordan R. ; Mahoney, Celia R. ; Menis, Sergey ; Mullen, Tina-Marie ; Karlsson Hedestam, Gunilla B. ; Maenza, Janine ; McDermott, Adrian B. ; Tomaras, Georgia D. ; Leggat, David J. ; Lombardo, Angela ; Eskandarzadeh, Saman ; Roederer, Mario ; Greene, Kelli ; Alavi, Nushin ; Fulp, William J. ; Laufer, Dagna S. ; Ballweber-Fleming, Lamar ; Corcoran, Martin M. ; McElrath, M. Juliana ; Brown, David M. ; Bethony, Jeffrey ; Williams, LaTonya D. ; Georgeson, Erik ; Groschel, Bettina
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 AS01
B
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.