![]() ![]() ![]() The details of the IRB/oversight body that provided approval or exemption for the research described are given below: ![]() I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. and by the Ragon Institute of MGH, MIT, and Harvard (to W.R.S.). and other support to W.R.S.), the IAVI Neutralizing Antibody Center (NAC) to W.R.S., National Institute of Allergy and Infectious Diseases (NIAID) P01 AI094419 (HIVRAD Optimizing HIV immunogen-BCR interactions for vaccine development") (to W.R.S.), UM1 Al100663 (Scripps Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery) and UM1 AI144462 (Scripps Consortium for HIV/AIDS Vaccine Development) (to W.R.S. This work was supported by the Bill and Melinda Gates Foundation Collaboration for AIDS Vaccine Discovery (CCVIMC INV-007371 to R.A.K., A.B.M., and M.J.M. and S.M are inventors on patents filed relating to the eOD-GT8 60mer immunogen in this manuscript. One-Sentence Summary Human genetic variation can modulate the strength of vaccine-induced broadly neutralizing antibody precursor B cell responses. ![]() The results demonstrate the need to define population-level immunoglobulin allelic variations when designing germline-targeting immunogens and evaluating them in clinical trials. 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. 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. Vaccine priming immunogens that activate germline precursors for broadly neutralizing antibodies (bnAbs) have promise for development of precision vaccines against major human pathogens. ![]()
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