High but Short-lived anti-SARS-CoV2 neutralizing, IgM, IgA, and IgG levels among mRNA-vaccinees compared to naturally-infected participants

1. Background Waning of protection against emerging SARS-CoV-2 variants by pre-existing antibodies elicited due to current vaccination or natural infection is a global concern. Whether this is due to waning of immunity to SARS-COV-2 remains unclear. Aim We aimed to investigate dynamics of antibody isotype responses among vaccinated naïve (VN) and naturally infected (NI) individuals. Methods We followed up antibody levels in COVID-19 mRNA-vaccinated subjects without prior infection (VN, n=100) at two phases: phase-I (P-I) at ∼1.4 and phase-II (P-II) at ∼5.3 months. Antibody levels were compared to those of unvaccinated and naturally infected subjects (NI, n=40) at ∼1.7 (P-1) and 5.2 (P-II) months post-infection. Neutralizing antibodies (NTAb), anti-S-RBD-IgG, -IgM, and anti-S-IgA isotypes were measured. Results VN group produced significantly greater antibody responses ( p <0.001) than NI group at P-I except for IgM. In VN group, a significant waning in antibody response was observed in all isotypes. There was about ∼ a 4-fold decline in NTAb levels ( p <0.001), anti-S-RBD-IgG (∼5-folds, p <0.001), anti-S-RBD-IgM (∼6-folds, p <0.001), and anti-S1-IgA (2-folds, p <0.001). In NI group, a significant but less steady decline was notable in NTAb (∼1-folds, p <0.001), anti-S-RBD IgG (∼1-fold, p =0.005), and S-RBD-IgM (∼2-folds, p <0.001). Unlike VN group, NI group mounted a lasting anti-S1-IgA response with no significant decline. Anti-S1-IgA levels which were ∼3 folds higher in VN subjects compared to NI in P-1 ( p <0.001), dropped to almost same levels, with no significant difference observed between the two groups in P-II. Conclusion While double dose mRNA vaccination boosted antibody levels, this “boost” was relatively short-lived in vaccinated individuals.