Mechanistic modeling projections of antibody persistence after homologous booster regimens of COVID‐19 vaccine Ad26.COV2.S in humans

Mechanistic model‐based simulations can be deployed to project the persistence of humoral immune response following vaccination. We used this approach to project the antibody persistence through 24 months from the data pooled across five clinical trials in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2)‐seronegative participants following vaccination with Ad26.COV2.S (5 × 10(10) viral particles), given either as a single‐dose or a homologous booster regimen at an interval of 2, 3, or 6 months. Antibody persistence was quantified as the percentage of participants with detectable anti‐spike binding and wild‐type virus neutralizing antibodies. The projected overall 24‐month persistence after single‐dose Ad26.COV2.S was 70.5% for binding antibodies and 55.2% for neutralizing antibodies, and increased after any homologous booster regimen to greater than or equal to 89.9% for binding and greater than or equal to 80.0% for neutralizing antibodies. The estimated model parameters quantifying the rates of antibody production attributed to short‐lived and long‐lived plasma cells decreased with increasing age, whereas the rate of antibody production mediated by long‐lived plasma cells was higher in women relative to men. Accordingly, a more pronounced waning of antibody responses was predicted in men aged greater than or equal to 60 years and was markedly attenuated following any homologous boosting regimen. The findings suggest that homologous boosting might be a viable strategy for maintaining protective effects of Ad26.COV2.S for up to 24 months following prime vaccination. The estimation of mechanistic modeling parameters identified the long‐lived plasma cell pathway as a key contributor mediating antibody persistence following single‐dose and homologous booster vaccination with Ad26.COV2.S in different subgroups of recipients stratified by age and sex.