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