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