SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback

Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection remains unclear. We evaluated the effect of infusion of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of MBCs targeting spike toward non-RBD epitopes. Furthermore, the relative affinity of RBD MBCs was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA coronavirus disease 2019 vaccination, MBC differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating MBC responses to infection, and single mAb administration can continue to impact MBC responses to additional antigen exposures months later. We report for the first time the effect of monoclonal antibody (mAb) treatment on SARS-CoV-2-specific human memory B cells of SARS-CoV-2-infected humans receiving, or not receiving, mRNA immunization. Our data show that mAb treatment alters later immune memory responses to vaccination.