High-resolution kinetics and cellular determinants of antibody response to SARS-CoV-2 over two years after COVID-19 vaccination

Abstract Despite widespread COVID-19 vaccine coverage, breakthrough infections are increasing, mainly driven by waning immunity and the emergence of SARS-CoV-2 Omicron variants. Here, we characterized the IgM, IgA and IgG kinetics in 55 visits over two years post-COVID-19 vaccination, and T-cell responses six months post-booster, in 31 healthy adults. Antibodies to Wuhan SARS-CoV-2 antigens and Alpha, Delta and Omicron variants were quantified by Luminex. SARS-CoV-2-specific T-cell responses were measured by activation-induced marker (AIM) and IFN-γ/IL-2 FluoroSpot assays. Antibody trajectories varied among isotypes. IgG decayed slowly during the first months and subsequently slowed down. IgA exhibited a rapid initial decay rate that decelerated stabilizing above the seropositivity threshold. Contrarily, IgM rapidly dropped to undetectable levels after primary vaccination. Importantly, three vaccine doses induced higher and more persistent anti-spike (S) IgG and IgA compared to two doses, whereas infection led to superior and longer-lasting IgG and IgA anti-S compared to three or two vaccine doses. Antibody levels to Omicron subvariants had shorter persistence than to ancestral virus. Finally, polyfunctional T cells correlated positively with subsequent IgA responses. These results revealed distinct isotype kinetics with non-constant decay rate and highlighted the benefits of booster doses in enhancing and sustaining antibody responses