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

Jeong Hyun Lee; Laura Toy; Justin T Kos; Yana Safonova; William R Schief; Colin Havenar-Daughton; Corey T Watson; Shane Crotty

doi:10.1038/s41541-021-00376-7

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

NPJ Vaccines. 2021 Sep 6;6(1):113. doi: 10.1038/s41541-021-00376-7.

Authors

Jeong Hyun Lee^{1

2}, Laura Toy^{1

2}, Justin T Kos³, Yana Safonova^{3

4}, William R Schief^{2

5

6

7}, Colin Havenar-Daughton^{1

2}, Corey T Watson⁸, Shane Crotty^{9

10

11}

Affiliations

¹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA.
² Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA.
³ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA.
⁴ Computer Science and Engineering Department, University of California San Diego, San Diego, CA, USA.
⁵ International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA, USA.
⁶ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
⁷ Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
⁸ Department of Biochemistry and Molecular Genetics, University of Louisville School of Medicine, Louisville, KY, USA. corey.watson@louisville.edu.
⁹ Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla, CA, USA. shane@lji.org.
¹⁰ Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA, USA. shane@lji.org.
¹¹ Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego (UCSD), La Jolla, CA, USA. shane@lji.org.

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.

Abstract

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