ABSTRACT
During the COVID-19 pandemic, numerous new SARS-CoV-2 variants of concern (VOC) evolved, many of which escape from antibody responses. Vaccination of COVID-19 convalescent individuals induces antibody responses of superior quantity and quality, which may even neutralize new VOC. We analyzed memory B cells (MBC) from convalescent donors and studied their involvement in COVID-19 vaccine responses. By expressing monoclonal antibodies from immunoglobulin V(D)J sequences of MBC and reverting their somatic hypermutations (SHM) to germline codes, we found that antibody maturation is crucial for the cross-neutralization of VOC. Infection-induced MBC substantially contributed to the subsequent vaccine response. A few dominant clonotypes that used characteristic VH gene segments and that diversified through SHM constituted a large fraction of the responding B cells. Analysis of functional consequences revealed that certain SHM contribute to the formation of an anticipatory memory that is suitable to neutralize virus variants that might emerge in the future.