Abstract
Understanding immune responses after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection will facilitate the development of next-generation vaccines. Here, we profiled spike (S)-specific B cell responses after Omicron/BA.1 infection in messenger RNA-vaccinated donors. The acute antibody response was characterized by high levels of somatic hypermutation and a bias toward recognition of ancestral SARS-CoV-2 strains, suggesting the early activation of vaccine-induced memory B cells. BA.1 breakthrough infection induced a shift in B cell immunodominance hierarchy from the S2 subunit, which is highly conserved across SARS-CoV-2 variants of concern (VOCs), and toward the antigenically variable receptor binding domain (RBD). A large proportion of RBD-directed neutralizing antibodies isolated from BA.1 breakthrough infection donors displayed convergent sequence features and broadly recognized SARS-CoV-2 VOCs. Together, these findings provide insights into the role of preexisting immunity in shaping the B cell response to heterologous SARS-CoV-2 variant exposure.
【초록키워드】 severe acute respiratory syndrome coronavirus 2, neutralizing antibody, SARS-CoV-2, coronavirus, immune response, Vaccines, Neutralizing antibodies, Antibody Response, SARS-CoV-2 variant, Infection, memory B cells, severe acute respiratory syndrome Coronavirus, omicron, Receptor binding domain, B cell, SARS-CoV-2 variants, RBD, immune responses, VOCs, understanding, Breakthrough infection, donors, respiratory, immunodominance, S2 subunit, Preexisting immunity, Heterologous, Donor, B cell response, Messenger RNA, acute respiratory syndrome, Activation, Recognition, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, sequence, shift, SARS-CoV-2 strains, feature, conserved, proportion, facilitate, characterized, 【제목키워드】 B cell memory, cross-reactive,