Modeling Antibody Kinetics Post-mRNA Booster Vaccination and Protection Durations Against SARS-CoV-2 Infection

Abstract

Understanding the dynamics of SARS-CoV-2 antibody levels post-booster vaccination is important to inform their durations of protection. Longitudinal antibody data was collected on the day of booster vaccination, as well as 28, 180, and 360 days after. Using nonlinear mixed effects models, we mapped the kinetics of binding IgA and IgG against wild-type (WT) and Omicron BA.1 spike proteins. Furthermore, we analyzed the association between antibody levels and risk of SARS-CoV-2 vaccine breakthrough infection through survival analyzes, and predicted durations of protection against infection. We found that the antibody response waned more rapidly following the Pfizer/BioNTech BNT162b2 booster compared to the Moderna mRNA-1273 booster. However, individuals boosted with the Pfizer vaccine exhibited a steeper rebound in antibody levels after infection. Faster postinfection antibody growth rates were observed in the elderly, females, and those with late infections. High antibody levels for WT IgG and BA.1 IgA at day 28 post-booster were associated with reduced infection risk; hazard ratios were 0.47 (95% CI [0.22, 0.98]) and 0.36 (95% CI [0.17, 0.78]), respectively, compared to low levels. Time-varying antibody levels showed better survival model fits. At medium COVID-19 case incidence (621 cases per million per day), a binding BA.1 IgA response of at least 20% is needed to sustain 80% protection against infection over 155 days post-booster. Our estimates of protection durations against SARS-CoV-2 infection post-booster vaccination may help inform the ideal frequency of boosters.