ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1622122
Identification of novel genetic biomarkers for ChAdOx1 nCoV-19 mediated immunogenicity
Provisionally accepted
Wan-Hsuan Chou1
Che-Mai Chang1Jafit Ting1Min-Rou Lin1Hsin-Ni Liao1Yi-Chien Chou1Chun-Yu Wei1Hsin-Hui Chi1Szu-Ying Ho1
Wei-Tzu Luo1Cheng-Lin Tsai1Ching-Hsuan Chao1Lu-Chun Chen1Tsung-Hsun Wu1Wei-Chih Liu1
Quynh Anh Nguyen1Hui-Wen Chang1Ching-Sheng Hung2
Shiao-Ya Hong3Jude Chu-Chun Wang4Shih-Hsin Hsiao1*
Wei-Chiao Chang1*- 1Taipei Medical University, Taipei, Taiwan
- 2Wan Fang Hospital, Taipei, Taiwan
- 3National Yang Ming Chiao Tung University, Taipei, Taiwan
- 4Taipei Medical University Hospital, Taipei, Taiwan
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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 Taiwan population.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).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 (ρlowPGS = -0.5 , ρmediumPGS = -0.2 , ρhighPGS = -0.0072).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.
Keywords: polygenic effect, host factors, COVID-19 vaccine responses, Genomics, biomarker
Received: 02 May 2025; Accepted: 02 Sep 2025.
Copyright: © 2025 Chou, Chang, Ting, Lin, Liao, Chou, Wei, Chi, Ho, Luo, Tsai, Chao, Chen, Wu, Liu, Nguyen, Chang, Hung, Hong, Wang, Hsiao and Chang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Shih-Hsin Hsiao, Taipei Medical University, Taipei, Taiwan
Wei-Chiao Chang, Taipei Medical University, Taipei, Taiwan
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