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- Title
Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming.
- Authors
deCamp, Allan C.; Corcoran, Martin M.; Fulp, William J.; Willis, Jordan R.; Cottrell, Christopher A.; Bader, Daniel L. V.; 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
- 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.
- Subjects
IMMUNOGLOBULIN genes; IMMUNOGLOBULIN heavy chains; HUMAN genes; B cells; VACCINE development
- Publication
NPJ Vaccines, 2024, Vol 9, Issue 1, p1
- ISSN
2059-0105
- Publication type
Article
- DOI
10.1038/s41541-024-00811-5