Modeling of anti-spike IgG and neutralizing antibody waning after anti-SARS-CoV-2 mRNA vaccination

Abstract

At present, mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are being administered on a global scale. While the efficacy of mRNA vaccines has been demonstrated, several unknowns remains. For example, as the number of booster vaccinations increases, there are uncertainties regarding how long effects of a vaccine will last and how much individual variability exists. In this study, to predict the duration of vaccine efficacy, we modeled the kinetics of antibody levels for each SARS-CoV-2 vaccination dose, incorporating predictive intervals to estimate the duration of vaccine efficacy and to account for variability among individuals. A total of 3,059 serum samples from 1,346 participants were assayed to quantify IgG antibodies specific for the S1 subunit of the S protein (anti-S1 IgG) and neutralizing antibody activities against SARS-CoV-2. A power law model was used to simulate the decay of antibody titers following vaccination, and models were constructed to assess antibody level kinetics after the second, third, fourth, and fifth vaccinations. The models assumed that booster vaccinations would significantly reduce the decline in anti-S antibody and neutralizing antibody levels, resulting in levels being maintained for a longer period. No significant differences in the decay rate of antibody levels were observed among age groups, yet the peak titers of antibody levels were significantly higher in the ≤ 39 age group than in the ≥ 60 age group following the second vaccination; these differences were not observed after the third and fourth vaccinations. The modeling of antibody level kinetics after vaccination is considered to be useful for understanding the immune status of mRNA vaccine recipients.