Vaccination induces HIV broadly neutralizing antibody precursors in humans

Authors

David J. Leggat, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Kristen W. Cohen, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Jordan R. Willis, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
William J. Fulp, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Allan C. deCamp, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Oleksandr Kalyuzhniy, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Christopher A. Cottrell, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Sergey Menis, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Greg Finak, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Lamar Ballweber-Fleming, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Abhinaya Srikanth, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Jason R. Plyler, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Torben Schiffner, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Alessia Liguori, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.
Farhad Rahaman, IAVI, New York, NY 10004, USA.
Angela Lombardo, IAVI, New York, NY 10004, USA.
Vincent Philiponis, IAVI, New York, NY 10004, USA.
Rachael E. Whaley, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Aaron Seese, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Joshua Brand, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Alexis M. Ruppel, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Wesley Hoyland, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Nicole L. Yates, Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
LaTonya D. Williams, Center for Human Systems Immunology, Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University, Durham, NC 27701, USA.
Kelli Greene, Duke University Medical Center, Durham, NC 27701, USA.
Hongmei Gao, Duke University Medical Center, Durham, NC 27701, USA.
Celia R. Mahoney, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA 98109, USA.
Martin M. Corcoran, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Alberto Cagigi, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Alison Taylor, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
David M. Brown, The Foundation for the National Institutes of Health, North Bethesda, MD 20852, USA.
David R. Ambrozak, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Document Type

Journal Article

Publication Date

12-2-2022

Journal

Science (New York, N.Y.)

Volume

378

Issue

6623

DOI

10.1126/science.add6502

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 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.

APA Citation

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.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2147

Department

Radiology