Effects of prior COVID-19 infection on B cell repertoire response to SARS-CoV-2 vaccination

We sequenced the B cell receptor repertoire (heavy-chain) of individuals undergoing vaccination by SARS-CoV-2 mRNA vaccine (Comirnaty/Pfizer/BNT162b2) with (seropositive) or without (seronegative) previous laboratory confirmed COVID-19 infection. We characterized differential isotype usage, V gene usage, HCD3R length, percentage of somatic hypermutation, and clonotype diversity. Only somatic hypermutation showed differential response to vaccination. We then characterized vaccine-expanded clonotypes and found that seropositive vaccine-expanded clonotypes had higher somatic hypermutation than seronegative vaccine-expanded clonotypes; and expanded clone groups for both serotypes had CDR3 lengths that were shorter than the rest of the repertoire. Moreover, in both groups we identified public clonotypes that were shared (2 or more individuals), including 28 clonotypes that were present in every sample tested in this study. We aligned HCDR3 regions of shared clonotypes and vaccine-expanded clonotypes to the Covid antibody data base (CoV-ab-dab) and had multiple matches, indicating clonal convergence in response to the vaccine.