Long-lasting antibody B-cell responses to SARS-CoV-2 three years after the onset of the pandemic.

Immune memory is essential for the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. In the current context of the pandemic, with a diminished vaccine efficacy against emerging variants, it remains crucial to perform long-term studies to evaluate the durability and quality of immune responses. Here, we examined the antibody and memory B-cell responses in a cohort of 113 healthcare workers with distinct exposure histories over a 3-year period. Previously infected and naive participants developed comparable humoral responses by 17 months after receiving a full three-dose mRNA vaccination. In addition, both maintained a substantial SARS-CoV-2-reactive memory B-cell pool, associated with a lower incidence of breakthrough infections in naive participants. Of note, previously infected participants developed an expanded SARS-CoV-2-reactive CD27^-CD21^- atypical B-cell population that remained stable throughout the follow-up period. Thus, previous SARS-CoV-2 infection differentially imprints the memory B-cell compartment without compromising the development of long-lasting humoral responses.