Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants.

The emergence of SARS-CoV-2 variants is jeopardizing the effectiveness of current vaccines and limiting the application of monoclonal antibody-based therapy for COVID-191,2. Here we analysed at single-cell level the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to dissect the nature of the B cell and antibody response. Almost six-thousands cells were sorted, over three-thousand of them produced monoclonal antibodies against the spike protein and more than four hundred neutralized the original Wuhan SARS-CoV-2 virus. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants showed to escape almost seventy per cent of these antibodies while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescent people and generated potent and broadly neutralizing antibodies. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants.