B cell receptor repertoire dynamics and convergent evolution following SARS-CoV-2 vaccination

• Published in: The Journal of immunology (1950) Vol. 208; no. 1_Supplement; pp. 65 - 65.10
• Main Authors: Fraley, Elizabeth Ross, Khanal, Santosh, LeMaster, Cas, Pierce, Stephen, Pastinen, Tomi, Bradley, Todd
• Format: Journal Article
• Language: English
• Published: 01.05.2022
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.208.Supp.65.10

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel betacoronavirus causing Coronavirus disease 2019 (COVID-19). B cell receptors (BCRs) are expressed at the surface of the B cell and are secreted as soluble antibodies. These antibodies can block viral infection by neutralizing the virus, are critical for resolution of SARS-CoV-2 infection, and may be correlates of protection for COVID-19 vaccines. We have previously shown that SARS-CoV-2 immunization elicits a robust antibody response that is significantly higher in individuals who recovered from COVID-19. Moreover, recovered individuals had slower antibody decay in their levels seven months after vaccination. Here, we sequenced the BCR repertoire of individuals undergoing vaccination by SARS-CoV-2 mRNA vaccine (Pfizer, BNT162b2) with (seropositive) or without (seronegative) previous laboratory confirmed COVID-19 infection. We identified genetic differences in the BCR repertoire between groups including V gene usage, CD3R length, percentage of somatic hypermutation, and clonotype diversity. We then focused our analyses to vaccine-expanded clonotypes in both groups to further analyze the differences in BCR repertoire on candidate SARS-CoV-2-specific clonotypes. We determined the frequency of pre-existing clones present after infection that were engaged by the vaccine in the seropositive group. Moreover, in both groups we identified clonotypes that were shared among individuals that could be a result of convergent evolution. Defining the characteristics and evolution of the BCR repertoire during vaccination of individuals with different histories of viral infection will aid in understanding SARS-CoV-2 humoral response dynamics.