Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

Background. The mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses. Methods. We here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations. Findings. Our findings show a robust immune response to the Spike proteins RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose. Interpretation. The Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine. Funding. The study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.