Genetic Variability in SARS-CoV-2 Vaccine Response: Association of rs3824949 in TRIM5 With Antibody Titers in a Japanese Cohort

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Individual immune responses to SARS-CoV-2 vaccination vary considerably; however, the genetic factors influencing antibody production remain incompletely understood.This study investigated the association between genetic polymorphisms and anti-SARS-CoV-2 antibody levels in 405 healthy Japanese individuals three weeks after their first dose of an mRNA vaccine.We focused on three genetic polymorphisms previously associated with antibody responses in humans.The GG genotype of rs3824949 in TRIM5 was significantly associated with higher antibody titers (P = 0.0009), whereas rs4792800 in TNFRSF13B and rs1611350 in HLA-F-AS1 showed no significant associations.Stepwise regression analysis confirmed that rs3824949 remained an independent predictor after adjusting for age, lymphocyte count, and platelet count.Given the role of TRIM5 in innate immunity, our findings suggest that rs3824949 may enhance immune responses to SARS-CoV-2 mRNA vaccination, highlighting the role of host genetics in individual variability in vaccine responses.By identifying a genetic factor that significantly influences antibody responses, this study lays the groundwork for personalized vaccine strategies tailored to individual genetic backgrounds.Moreover, these findings may have broader implications beyond SARS-CoV-2, informing the design and optimization of future mRNA vaccines targeting other infectious diseases or cancers.Our work highlights the potential of precision vaccinology and emphasizes the need to include ethnically diverse populations in immunogenetic research.These insights contribute to a more equitable and effective global vaccination strategy, particularly in the era of rapidly advancing mRNA vaccine technologies.

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