Details

Autor(en) / Beteiligte

• 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
• 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
• Kolokythas, Orpheus
• Khati, Nadia
• Bethony, Jeffrey
• Roederer, Mario
• Diemert, David
• Koup, Richard A
• Laufer, Dagna S
• McElrath, Juliana M
• McDermott, Adrian B
• Karlsson Hedestam, Gunilla B
• Schief, William R

Titel

Human immunoglobulin gene allelic variation impacts germline-targeting vaccine priming

Ist Teil von

• npj vaccines, 2024-03, Vol.9 (1), p.58-13, Article 58

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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.