B cell receptor repertoire kinetics after SARS-CoV-2 infection and vaccination
Prasanti Kotagiri, Federica Mescia, William Rae, Laura Bergamaschi, Zewen Kelvin Tuong, Lorinda Turner, Kelvin Hunter, Pehuén Pereyra Gerber, Myra Hosmillo, Christoph Hess, Menna R. Clatworthy, Ian Goodfellow, Nicholas J. Matheson, Eoin McKinney, Mark R. Wills, Ravindra K. Gupta, John R. Bradley, Rachael Bashford-Rogers, Paul Lyons, Kenneth G. C. Smith
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.