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

Abstract 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...

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Autores principales:	Jeong Hyun Lee, Laura Toy, Justin T. Kos, Yana Safonova, William R. Schief, Colin Havenar-Daughton, Corey T. Watson, Shane Crotty
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/996c49bfefaf45c393289c1cfe6ce853
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spelling	oai:doaj.org-article:996c49bfefaf45c393289c1cfe6ce8532021-12-02T17:41:16ZVaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells10.1038/s41541-021-00376-72059-0105https://doaj.org/article/996c49bfefaf45c393289c1cfe6ce8532021-09-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00376-7https://doaj.org/toc/2059-0105Abstract 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.Jeong Hyun LeeLaura ToyJustin T. KosYana SafonovaWilliam R. SchiefColin Havenar-DaughtonCorey T. WatsonShane CrottyNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Jeong Hyun Lee Laura Toy Justin T. Kos Yana Safonova William R. Schief Colin Havenar-Daughton Corey T. Watson Shane Crotty Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
description	Abstract 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.
format	article
author	Jeong Hyun Lee Laura Toy Justin T. Kos Yana Safonova William R. Schief Colin Havenar-Daughton Corey T. Watson Shane Crotty
author_facet	Jeong Hyun Lee Laura Toy Justin T. Kos Yana Safonova William R. Schief Colin Havenar-Daughton Corey T. Watson Shane Crotty
author_sort	Jeong Hyun Lee
title	Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
title_short	Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
title_full	Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
title_fullStr	Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
title_full_unstemmed	Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells
title_sort	vaccine genetics of ighv1-2 vrc01-class broadly neutralizing antibody precursor naïve human b cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/996c49bfefaf45c393289c1cfe6ce853
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Vaccine genetics of IGHV1-2 VRC01-class broadly neutralizing antibody precursor naïve human B cells

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