Effects of Prior Infection with SARS-CoV-2 on B Cell Receptor Repertoire Response during Vaccination

Understanding the B cell response to SARS-CoV-2 vaccines is a high priority. High-throughput sequencing of the B cell receptor (BCR) repertoire allows for dynamic characterization of B cell response. Here, we sequenced the BCR repertoire of individuals vaccinated by the Pfizer SARS-CoV-2 mRNA vaccine. We compared BCR repertoires of individuals with previous COVID-19 infection (seropositive) to individuals without previous infection (seronegative). We discovered that vaccine-induced expanded IgG clonotypes had shorter heavy-chain complementarity determining region 3 (HCDR3), and for seropositive individuals, these expanded clonotypes had higher somatic hypermutation (SHM) than seronegative individuals. We uncovered shared clonotypes present in multiple individuals, including 28 clonotypes present across all individuals. These 28 shared clonotypes had higher SHM and shorter HCDR3 lengths compared to the rest of the BCR repertoire. Shared clonotypes were present across both serotypes, indicating convergent evolution due to SARS-CoV-2 vaccination independent of prior viral exposure.