npj Vaccines (Mar 2024)
Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming
- Allan C. deCamp,
- Martin M. Corcoran,
- William J. Fulp,
- Jordan R. Willis,
- Christopher A. Cottrell,
- Daniel L. V. Bader,
- Oleksandr Kalyuzhniy,
- David J. Leggat,
- Kristen W. Cohen,
- Ollivier Hyrien,
- Sergey Menis,
- Greg Finak,
- Lamar Ballweber-Fleming,
- Abhinaya Srikanth,
- Jason R. Plyler,
- Farhad Rahaman,
- Angela Lombardo,
- Vincent Philiponis,
- Rachael E. Whaley,
- Aaron Seese,
- Joshua Brand,
- Alexis M. Ruppel,
- Wesley Hoyland,
- Celia R. Mahoney,
- Alberto Cagigi,
- Alison Taylor,
- David M. Brown,
- David R. Ambrozak,
- Troy Sincomb,
- Tina-Marie Mullen,
- Janine Maenza,
- Orpheus Kolokythas,
- Nadia Khati,
- Jeffrey Bethony,
- Mario Roederer,
- David Diemert,
- Richard A. Koup,
- Dagna S. Laufer,
- Juliana M. McElrath,
- Adrian B. McDermott,
- Gunilla B. Karlsson Hedestam,
- William R. Schief
Affiliations
- Allan C. deCamp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Martin M. Corcoran
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
- William J. Fulp
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Jordan R. Willis
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Christopher A. Cottrell
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Daniel L. V. Bader
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Oleksandr Kalyuzhniy
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- David J. Leggat
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Kristen W. Cohen
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Ollivier Hyrien
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Sergey Menis
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Greg Finak
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Lamar Ballweber-Fleming
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Abhinaya Srikanth
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Jason R. Plyler
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Farhad Rahaman
- IAVI, 125 Broad Street, 9th floor
- Angela Lombardo
- IAVI, 125 Broad Street, 9th floor
- Vincent Philiponis
- IAVI, 125 Broad Street, 9th floor
- Rachael E. Whaley
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Aaron Seese
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Joshua Brand
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Alexis M. Ruppel
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Wesley Hoyland
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Celia R. Mahoney
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Alberto Cagigi
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Alison Taylor
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- David M. Brown
- The Foundation for the National Institutes of Health
- David R. Ambrozak
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Troy Sincomb
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Tina-Marie Mullen
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- Janine Maenza
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Orpheus Kolokythas
- Department of Radiology, University of Washington
- Nadia Khati
- Department of Radiology, School of Medicine and Health Sciences, The George Washington University
- Jeffrey Bethony
- Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University
- Mario Roederer
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- David Diemert
- Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, The George Washington University
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Dagna S. Laufer
- IAVI, 125 Broad Street, 9th floor
- Juliana M. McElrath
- Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center
- Adrian B. McDermott
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Gunilla B. Karlsson Hedestam
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet
- William R. Schief
- IAVI Neutralizing Antibody Center, The Scripps Research Institute
- DOI
- https://doi.org/10.1038/s41541-024-00811-5
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 13
Abstract
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.
