학술논문
Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming
Document Type
article
Author
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
Source
npj Vaccines, Vol 9, Iss 1, Pp 1-13 (2024)
Subject
Language
English
ISSN
2059-0105
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.