Identification of novel genetic biomarkers for ChAdOx1 nCoV-19 mediated immunogenicity

Background: Research comprehensively examining factors for COVID-19 DNA vaccine responses is lacking, particularly in Asian populations. This study aims to investigate biomarkers of reactogenic and immunogenic responses after DNA-based COVID-19 vaccination in a Taiwanese population. Methods: A genome-wide association study (GWAS) of 415 Taiwanese healthcare workers was conducted to identify genetic variants associated with reactogenic and immunogenic responses to the first and second doses of ChAdOx1 nCoV-19 vaccine. Furthermore, gene set enrichment analysis was conducted to elucidate the underlying biological pathways. Finally, a polygenic score (PGS) was utilized to assess the synergistic host effects on neutralizing antibody (NT50). Results: We identified 501 suggestive significant genetic associations with vaccine responses, enriched in lipid and lipophilic vitamin metabolism, interleukin signaling, and neurotransmitter release pathways. Moreover, we observed a combined effect of genetics with age and sex on NT50 after the second dose. Notably, the negative correlation between age and NT50 was stronger in lower PGS groups (ρ_lowPGS = -0.5, ρ_mediumPGS = -0.2, ρ_highPGS = -0.0072). Conclusion: Our study fills a critical gap by addressing the lack of research on genetic factors of ChAdOx1 nCoV-19 vaccine responses in Asian population, providing valuable insights into the genetic basis of DNA-based vaccine responses. The synergic host effect highlights the value of integrating genetic information with other host factors as a biomarker to predict individual vaccine responses. Our findings can contribute to personalized vaccination strategies and future vaccination policies.