SARS-CoV-2 booster vaccine dose significantly extends humoral immune response half-life beyond the primary series

Abstract

SARS-CoV-2 lipid nanoparticle mRNA therapeutics continue to be administered as the predominant therapeutic intervention to reduce COVID-19 disease pathogenesis. Quantifying the kinetics of the secondary immune response from subsequent doses beyond the primary series, and understanding how dose-dependent immune waning kinetics vary as a function of age, sex, and various comorbidities, remains an important question. We study anti-spike IgG waning kinetics in 152 individuals who received an mRNA-based primary series and a subset of 137 individuals who then received a booster dose. We find the booster dose elicits a 71-84\% increase in the median Anti-S half life over that of the primary series. We find the Anti-S half life for both primary series and booster doses drops as a function of increased year of age. However, we stress that although chronological age continues to be a good proxy for vaccine-induced humoral waning, immunosenescence is likely not the mechanism, rather, more likely the mechanism is related to the presence of noncommunicable diseases, which also accumulate with age, that affect immune regulation. We are able to independently reproduce recent observations that those with pre-existing asthma exhibit a stronger primary series humoral response to vaccination than compared to those that do not, and further find this result is sustained for the booster dose. Finally, via a single-variate Kruskal-Wallis Test we find no difference between male and female decay kinetics, however, a multivariate approach utilizing Lasso regression for feature selection reveals a statistically significant (p-value <10^-3), albeit small, bias in favour of longer-lasting humoral immunity amongst males.