Vaccination induces HIV broadly neutralizing antibody precursors in humans.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Leggat, DJ; Cohen, KW; Willis, JR; Fulp, WJ; deCamp, AC; Kalyuzhniy, O; Cottrell, CA; Menis, S; Finak, G; Ballweber-Fleming, L; Srikanth, A; Plyler, JR; Schiffner, T; Liguori, A; Rahaman, F; Lombardo, A; Philiponis, V; Whaley, RE; Seese, A; Brand, J; Ruppel, AM; Hoyland, W; Yates, NL; Williams, LD; Greene, K; Gao, H; Mahoney, CR; Corcoran, MM; Cagigi, A; Taylor, A; Brown, DM; Ambrozak, DR; Sincomb, T; Hu, X; Tingle, R; Georgeson, E; Eskandarzadeh, S; Alavi, N; Lu, D; Mullen, T-M; Kubitz, M; Groschel, B; Maenza, J; Kolokythas, O; Khati, N; Bethony, J; Crotty, S; Roederer, M; Karlsson Hedestam, GB; Tomaras, GD; Montefiori, D; Diemert, D; Koup, RA; Laufer, DS; McElrath, MJ; McDermott, AB; Schief, WR

Published Date

  • December 2, 2022

Published In

Volume / Issue

  • 378 / 6623

Start / End Page

  • eadd6502 -

PubMed ID

  • 36454825

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.add6502


  • eng

Conference Location

  • United States