BNT162b2 vaccine induces divergent B cell responses to SARS-CoV-2 S1 and S2

The first ever messenger RNA (mRNA) vaccines received emergency approvals in December 2020 and are highly protective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the contribution of each dose to the generation of antibodies against SARS-CoV-2 spike (S) protein and the degree of protection against novel variants warrant further study. Here, we investigated the B cell response to the BNT162b2 vaccine by integrating B cell repertoire analysis with single-cell transcriptomics pre and post vaccination. The first vaccine dose elicits a recall response of IgA+ memory B cells targeting the S subunit S2. Starting on day 21, and later boosted by the 2nd dose, minimally mutated activated switched memory B cells develop, most likely from naive B cells, which target the receptor binding domain (RBD) of the S1 subunit, and secrete IgG that potently neutralize several SARS-CoV-2 variants, including Delta.