The Human Genetic Differences in the Outcomes of mRNA Vaccination against COVID-19: A Prospective Cohort Study

Background: This study aimed to explore how genetic variations in individuals impact neutralization activity post-mRNA vaccination, recognizing the critical role vaccination plays in curbing COVID-19 spread and the necessity of ensuring vaccine efficacy amidst genetic diversity. Methods: In a 4-week clinical pilot study, 534 healthy subjects received their first COVID vaccine dose, followed by the second dose. Antibody levels were evaluated thrice. From this pool, 120 participants were selected and divided into high- and low-antibody groups based on their levels. Genomic DNA was isolated from peripheral blood mononuclear cells for pilot genome-wide association studies (GWAS) conducted on a single platform. Real-time PCR was used to confirm differences in gene expression identified via GWAS analysis. Results: Three SNPs exceeded the level of p < 1.0 × 10. The rs7795433 SNP of the HDAC9 gene (7q21.1) showed the strongest association with COVID-19 vaccination under the additive model (OR = 5.63; p = 3 × 10). In the PCR experiments, the AA genotype group showed that the gene expression level of HDAC9 was likely to be decreased in the low-antibody-formation group at the time of vaccination. Conclusion: We found that AA genotype holders (rs7795433 SNP of the HDAC9 gene) have a high probability of having a higher antibody count when vaccinated, and GG type holders have a high probability of the opposite. These findings show that the genetic characteristics of vaccinated people may affect antibody production after COVID vaccination.