Our findings reveal that mucosal vaccines induce robust mucosal immunity, particularly through secretory IgA, demonstrate a favorable safety profile with no increased risk of adverse events compared to intramuscular vaccines or placebo, and provide valid protective efficacy, with vaccine effectiveness (VE) of 35% (95% CI: 4–56%) for COVID-19 and 27% (95% CI: 13–41%) for influenza. This evidence concerns the gene CD79A and COVID-19.