B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination

Prasanti Kotagiri; Federica Mescia; William M Rae; Laura Bergamaschi; Zewen K Tuong; Lorinda Turner; Kelvin Hunter; Pehuén P Gerber; Myra Hosmillo; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Christoph Hess; Menna R Clatworthy; Ian G Goodfellow; Nicholas J Matheson; Eoin F McKinney; Mark R Wills; Ravindra K Gupta; John R Bradley; Rachael J M Bashford-Rogers; Paul A Lyons; Kenneth G C Smith

doi:10.1016/j.celrep.2022.110393

B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination

Cell Rep. 2022 Feb 15;38(7):110393. doi: 10.1016/j.celrep.2022.110393. Epub 2022 Jan 31.

Authors

Prasanti Kotagiri¹, Federica Mescia², William M Rae², Laura Bergamaschi², Zewen K Tuong³, Lorinda Turner², Kelvin Hunter², Pehuén P Gerber², Myra Hosmillo⁴; Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration; Christoph Hess⁵, Menna R Clatworthy⁶, Ian G Goodfellow⁴, Nicholas J Matheson⁷, Eoin F McKinney², Mark R Wills², Ravindra K Gupta², John R Bradley⁸, Rachael J M Bashford-Rogers⁹, Paul A Lyons¹⁰, Kenneth G C Smith¹¹

Affiliations

¹ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK. Electronic address: pk488@cam.ac.uk.
² Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK.
³ Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, Cambridge CB10 1RQ, UK.
⁴ Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
⁵ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK; Department of Biomedicine, University and University Hospital Basel, Basel 4031, Switzerland; Botnar Research Centre for Child Health (BRCCH) University Basel and ETH Zurich, Basel 4059, Switzerland.
⁶ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK; Cellular Genetics, Wellcome Sanger Institute, Hinxton, Cambridge CB10 1RQ, UK.
⁷ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK; NHS Blood and Transplant, Cambridge CB2 1PT, UK.
⁸ Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK; NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
⁹ Nuffield Department of Medicine, Wellcome Centre for Human Genetics, Oxford OX3 7BN, UK.
¹⁰ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK. Electronic address: pal34@cam.ac.uk.
¹¹ Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge CB2 0AW, UK; Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge CB2 0QQ, UK. Electronic address: kgcs2@cam.ac.uk.

Abstract

B cells are important in immunity to both severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and vaccination, but B cell receptor (BCR) repertoire development in these contexts has not been compared. We analyze serial samples from 171 SARS-CoV-2-infected individuals and 63 vaccine recipients and find the global BCR repertoire differs between them. Following infection, immunoglobulin (Ig)G1/3 and IgA1 BCRs increase, somatic hypermutation (SHM) decreases, and, in severe disease, IgM and IgA clones are expanded. In contrast, after vaccination, the proportion of IgD/M BCRs increase, SHM is unchanged, and expansion of IgG clones is prominent. VH1-24, which targets the N-terminal domain (NTD) and contributes to neutralization, is expanded post infection except in the most severe disease. Infection generates a broad distribution of SARS-CoV-2-specific clones predicted to target the spike protein, while a more focused response after vaccination mainly targets the spike's receptor-binding domain. Thus, the nature of SARS-CoV-2 exposure differentially affects BCR repertoire development, potentially informing vaccine strategies.

Keywords: B cell receptor repertoire; COVID-19; SARS-CoV-2 vaccination.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

B-Lymphocytes / immunology
BNT162 Vaccine / immunology
COVID-19 / immunology*
COVID-19 / prevention & control
Clonal Evolution
Humans
Immunoglobulin Heavy Chains / genetics
Immunoglobulin Heavy Chains / immunology
Immunoglobulin Isotypes / genetics
Immunoglobulin Isotypes / immunology
Immunoglobulin Variable Region / genetics
Immunoglobulin Variable Region / immunology
Kinetics
Receptors, Antigen, B-Cell / genetics
Receptors, Antigen, B-Cell / immunology*
SARS-CoV-2 / immunology
Severity of Illness Index
Somatic Hypermutation, Immunoglobulin / immunology
Spike Glycoprotein, Coronavirus / immunology
Vaccination*

Substances

Immunoglobulin Heavy Chains
Immunoglobulin Isotypes
Immunoglobulin Variable Region
Receptors, Antigen, B-Cell
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
BNT162 Vaccine

Abstract

Publication types

MeSH terms

Substances

Grants and funding