Purpose High-performance sports training has been associated with immunomodulatory activity on vaccine-induced immunity in athletes. To date, it is unknown whether training in athletes may affect immunogenicity of mRNA-based vaccines, as the vaccine antigen is produced in the muscle. Methods In an observational study, 57 athletes and 57 controls were recruited before and 2 weeks after the second vaccination with a COVID-19 mRNA vaccine. Spike-specific IgG antibodies were quantified using enzyme-linked immunosorbant assay. Quantitative and functional characterization of SARS-CoV-2-specific T cells was carried out from whole blood using flow cytometry. Adverse events within the first 7 days after the first and the second vaccination were self-reported using a diary. Results Levels of anti-spike IgG antibodies were similar in athletes (5766 (interquartile range, 4923) BAU·mL-1) and controls (6677 (interquartile range, 6741) BAU·mL-1, P = 0.317), which also held true for neutralizing activity (P = 0.185). In contrast, athletes reached significantly lower levels of spike-specific CD4 (P = 0.0001) and CD8 T cells (P = 0.025). Although most individuals from both groups had spike-specific CD4 T-cell levels above detection limit, the percentage of individuals with detectable CD8 T cells was significantly lower among athletes (23/57 (40.4%)) compared with controls (35/57 (61.4%), P = 0.039). Cytokine expression profiling showed no major differences between the groups, whereas the expression of CTLA-4 was significantly lower in spike-specific CD4 T cells of athletes. Overall, adverse events were similar among the groups except for more athletes reporting swelling at the injection site and headache. Conclusions COVID-19 mRNA vaccination was well tolerated and induced a strong humoral and cellular immune response in both athletes and controls. The significantly lower levels of vaccine-specific T cells with less CD8 T-cell responders among athletes may indicate mRNA vaccine-specific alterations in immune responses related to high-performance sports training.
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