Estimating the decay of protective antibodies induced by SARS-CoV-2 mRNA vaccination and hybrid immunity

Starting in 2020, we quantified anti-wildtype SARS-CoV-2 spike sera IgG at monthly intervals from generally healthy adults after various doses of mRNA-based COVID-19 vaccination and in the context of hybrid immunity. Confirmed post-vaccination infections and subclinical infections identified by longitudinal serology were removed from vaccine-only analyses. Over 400 days, the two-dose vaccine-alone antibody response decayed at a half-life (t_1/2) of 59.8 days compared with a t_1/2 of 99.7 days after receipt of one booster dose. In the hybrid immunity model, the t_1/2 was greater at 241 days. Using cut-offs for correlation of protection obtained in a prior study, we modeled that individuals with hybrid immunity maintain antibody levels above a 75% correlate of immunity for 283 days after an immune-boosting event. These data offer insights into SARS-CoV-2 antibody decay kinetics that may inform COVID-19 vaccine timing in the younger (age under 60), healthy adult population.