Pre-existing SARS-CoV-2 immunity influences potency, breadth, and durability of the humoral response to SARS-CoV-2 vaccination

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic highlights the importance of determining the breadth and durability of humoral immunity to SARS-CoV-2 mRNA vaccination. Herein, we characterize the humoral response in 27 naive and 40 recovered vaccinees. SARS-CoV-2-specific antibody and memory B cell (MBC) responses are durable up to 6 months, although antibody half-lives are shorter for naive recipients. The magnitude of the humoral responses to vaccination strongly correlates with responses to initial SARS-CoV-2 infection. Neutralization titers are lower against SARS-CoV-2 variants in both recovered and naive vaccinees, with titers more reduced in naive recipients. While the receptor-binding domain (RBD) is the main neutralizing target of circulating antibodies, Moderna-vaccinated naives show a lesser reliance on RBDs, with >25% neutralization remaining after depletion of RBD-binding antibodies. Overall, we observe that vaccination induces higher peak titers and improves durability in recovered compared with naive vaccinees. These findings have broad implications for current vaccine strategies deployed against the SARS-CoV-2 pandemic. [Display omitted] •Single vaccine dose effectively boosts B cell responses in recovered subjects•SARS-CoV-2-specific MBCs remain activated and increase over time in naive subjects•Antibody response to vaccination is broader and more durable in recovered versus naive subjects•Naive vaccinees have higher proportion of non-RBD-specific neutralizing antibodies Mantus et al. find that kinetics, breadth, and durability of humoral immune responses to mRNA vaccination are dependent on pre-existing immunity to SARS-CoV-2. Cellular and serological SARS-CoV-2-specific immunity is detected in both recovered and naive individuals after vaccination, with broader and more durable serological responses detected in recovered individuals.