Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming

Authors

• Allan C. deCamp, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA. adecamp@scharp.org.
• Martin M. Corcoran, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
• William J. Fulp, 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.
• Christopher A. Cottrell, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
• Daniel L. Bader, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
• Oleksandr Kalyuzhniy, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
• David J. Leggat, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Kristen W. Cohen, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
• Ollivier Hyrien, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, 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, USA.
• Jason R. Plyler, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Farhad Rahaman, IAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
• Angela Lombardo, IAVI, 125 Broad Street, 9th floor, New York, NY, 10004, USA.
• Vincent Philiponis, IAVI, 125 Broad Street, 9th floor, 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, USA.
• Alexis M. Ruppel, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Wesley Hoyland, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Celia R. Mahoney, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
• Alberto Cagigi, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Alison Taylor, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• David M. Brown, The Foundation for the National Institutes of Health, North Bethesda, MD, USA.
• David R. Ambrozak, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
• Troy Sincomb, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
• Tina-Marie Mullen, IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, 92037, USA.
• Janine Maenza, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, 98109, USA.
• Orpheus Kolokythas, Department of Radiology, University of Washington, Seattle, WA, 98195, USA.

Document Type

Journal Article

Publication Date

3-11-2024

Journal

NPJ vaccines

Volume

9

Issue

1

DOI

10.1038/s41541-024-00811-5

Abstract

Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. In a clinical trial of the eOD-GT8 60mer germline-targeting immunogen, higher frequencies of vaccine-induced VRC01-class bnAb-precursor B cells were observed in the high dose compared to the low dose group. Through immunoglobulin heavy chain variable (IGHV) genotyping, statistical modeling, quantification of IGHV1-2 allele usage and B cell frequencies in the naive repertoire for each trial participant, and antibody affinity analyses, we found that the difference between dose groups in VRC01-class response frequency was best explained by IGHV1-2 genotype rather than dose and was most likely due to differences in IGHV1-2 B cell frequencies for different genotypes. The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials.

APA Citation

deCamp, Allan C.; Corcoran, Martin M.; Fulp, William J.; Willis, Jordan R.; Cottrell, Christopher A.; Bader, Daniel L.; Kalyuzhniy, Oleksandr; Leggat, David J.; Cohen, Kristen W.; Hyrien, Ollivier; Menis, Sergey; Finak, Greg; Ballweber-Fleming, Lamar; Srikanth, Abhinaya; Plyler, Jason R.; Rahaman, Farhad; Lombardo, Angela; Philiponis, Vincent; Whaley, Rachael E.; Seese, Aaron; Brand, Joshua; Ruppel, Alexis M.; Hoyland, Wesley; Mahoney, Celia R.; Cagigi, Alberto; Taylor, Alison; Brown, David M.; Ambrozak, David R.; Sincomb, Troy; Mullen, Tina-Marie; Maenza, Janine; and Kolokythas, Orpheus, "Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming" (2024). GW Authored Works. Paper 4541.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4541

Department

Microbiology, Immunology, and Tropical Medicine