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.
Author list:
Affiliations
- 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
- Division of Virology, Department of Pathology, University of Cambridge, Addenbrooke’s Hospital, 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
- NHS Blood and Transplant, Cambridge CB2 1PT, UK
- NIHR BioResource, Cambridge University Hospitals NHS Foundation, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK
- Nuffield Department of Medicine, Wellcome Centre for Human Genetics, Oxford OX3 7BN, UK
Authors
Prasanti Kotagiri1,2,* Federica Mescia1,2 William M. Rae1,2 Laura Bergamaschi1,2 Zewen K. Tuong2,3 Lorinda Turner1,2 Kelvin Hunter1,2 Pehuén P. Gerber1,2 Myra Hosmillo4 Cambridge Institute of Therapeutic Immunology and Infectious Disease-National Institute of Health Research (CITIID-NIHR) COVID BioResource Collaboration, Christoph Hess1,2,5,6 Menna R. Clatworthy1,2,3 Ian G. Goodfellow,4 Nicholas J. Matheson1,2,7 Eoin F. McKinney1,2 Mark R. Wills1,2 Ravindra K. Gupta1,2 John R. Bradley2,8 Rachael J.M. Bashford-Rogers9 Paul A. Lyons1,2,* and Kenneth G.C. Smith1,2,*
