Vaccination induces HIV broadly neutralizing antibody precursors in humans
Science (New York, N.Y.)
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 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.
Leggat, David J.; Cohen, Kristen W.; Willis, Jordan R.; Fulp, William J.; deCamp, Allan C.; Kalyuzhniy, Oleksandr; Cottrell, Christopher A.; Menis, Sergey; Finak, Greg; Ballweber-Fleming, Lamar; Srikanth, Abhinaya; Plyler, Jason R.; Schiffner, Torben; Liguori, Alessia; Rahaman, Farhad; Lombardo, Angela; Philiponis, Vincent; Whaley, Rachael E.; Seese, Aaron; Brand, Joshua; Ruppel, Alexis M.; Hoyland, Wesley; Yates, Nicole L.; Williams, LaTonya D.; Greene, Kelli; Gao, Hongmei; Mahoney, Celia R.; Corcoran, Martin M.; Cagigi, Alberto; Taylor, Alison; Brown, David M.; and Ambrozak, David R., "Vaccination induces HIV broadly neutralizing antibody precursors in humans" (2022). GW Authored Works. Paper 2147.