{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:03:33Z","timestamp":1759190613611,"version":"3.44.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC114-2327-B-038-001, NSTC112-2320-B-038-026-MY3"],"award-info":[{"award-number":["NSTC114-2327-B-038-001, NSTC112-2320-B-038-026-MY3"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004700","name":"Taipei Medical University","doi-asserted-by":"publisher","award":["112-5812-004-400 (Yusuke Nakamura Chair Professorship)"],"award-info":[{"award-number":["112-5812-004-400 (Yusuke Nakamura Chair Professorship)"]}],"id":[{"id":"10.13039\/501100004700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010613","name":"Taipei Medical University Hospital","doi-asserted-by":"publisher","award":["111TMUH-NE-03"],"award-info":[{"award-number":["111TMUH-NE-03"]}],"id":[{"id":"10.13039\/501100010613","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 (\u03c1<jats:sub>lowPGS<\/jats:sub> = -0.5, \u03c1<jats:sub>mediumPGS<\/jats:sub> = -0.2, \u03c1<jats:sub>highPGS<\/jats:sub> = -0.0072).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1622122","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T05:25:28Z","timestamp":1759123528000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of novel genetic biomarkers for ChAdOx1 nCoV-19 mediated 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