Population homogeneity for the antibody response to COVID-19 BNT162b2 / Comirnaty vaccine is only reached after the second dose, across all adult age ranges

Abstract

ABSTRACT BACKGROUND While mRNA vaccines authorized for emergency use are administrated worldwide in an effort to contain the COVID-19 pandemic, little is known about the heterogeneity of the humoral immune response they induce at the population scale. METHODS We conducted a prospective observational longitudinal study in 1245 hospital care workers and 146 nursing home residents, together covering adult ages from 19 to 99 years. Blood samples were taken before vaccination, 3-5 weeks after the first vaccine dose, and 3 weeks after the second dose of BNT162b2 mRNA COVID-19 (Comirnaty, Pfizer/BioNTech). End points were seroconversion to SARS-CoV-2 spike protein and amount of spike-specific IgG, IgM and IgA following the first dose and the boosting effect of the second vaccination. We also addressed the effect of age, sex and pre-exposure to SARSCov-2 on these parameters. RESULTS Among 1067 baseline seronegative participants, seroconversion after the first vaccine dose varied from a maximum of 98,6% in the younger age strata [19-29 years] to a minimum of 25.4 % in the older age group [70-100 years], while sex had little effect. Large inter-individual variation in the amplitude of the antibody response were observed in all age strata. The second dose brought seroconversion to high frequency (100% and 94.9% in younger and older age strata, respectively) and homogenised IgG responses to high levels, while IgM and IgA levels remained low and heterogeneous. Previous exposure to SARS-Cov-2 boosted IgG level after a single injection. Seven non-responders were identified after the second dose. CONCLUSIONS In this large study, covering all adult age ranges, BNT162b2 vaccination resulted in isotypic and heterogeneous antibody responses, advocating for the interval between the two doses not to be extended and for serological monitoring of elderly and immunosuppressed vaccinees.