Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells

A successful HIV vaccine eliciting broadly neutralizing antibodies (bnAbs) must overcome the hurdle of being able to activate naive precursor B cells encoding features within their germline B cell receptors (BCR) that allow recognition of broadly neutralizing epitopes. Knowledge of whether bnAb prec...

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Bibliographic Details
Published in:npj vaccines 2021-09, Vol.6 (1), p.113-113, Article 113
Main Authors: Lee, Jeong Hyun, Toy, Laura, Kos, Justin T., Safonova, Yana, Schief, William R., Havenar-Daughton, Colin, Watson, Corey T., Crotty, Shane
Format: Article
Language:English
Subjects:
631/250/2152/2153
631/250/590/2294
Antibodies
Biomedical and Life Sciences
Biomedicine
Cellular biology
Genetics
Genotype & phenotype
HIV
Human immunodeficiency virus
Human populations
Infectious Diseases
Medical Microbiology
Public Health
Vaccine
Vaccines
Virology
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Summary:A successful HIV vaccine eliciting broadly neutralizing antibodies (bnAbs) must overcome the hurdle of being able to activate naive precursor B cells encoding features within their germline B cell receptors (BCR) that allow recognition of broadly neutralizing epitopes. Knowledge of whether bnAb precursor B cells are circulating at sufficient frequencies within individuals in communities heavily impacted by HIV may be important. Using a germline-targeting eOD-GT8 immunogen and high-throughput droplet-based single-cell BCR sequencing, we demonstrate that large numbers of paired BCR sequences from multiple donors can be efficiently screened to elucidate precursor frequencies of rare, naive VRC01-class B cells. Further, we analyzed IGHV1-2 allelic usage among three different cohorts; we find that IGHV1-2 alleles traditionally thought to be incompatible with VRC01-class responses are relatively common in various human populations and that germline variation within IGHV1-2 associates with gene usage frequencies in the naive BCR repertoire.
ISSN:2059-0105
2059-0105
DOI:10.1038/s41541-021-00376-7