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Front Immunol
. 2025 Sep 29:16:1622122.
doi: 10.3389/fimmu.2025.1622122. eCollection 2025. Identification of novel genetic biomarkers for ChAdOx1 nCoV-19 mediated immunogenicity
Wan-Hsuan Chou 1 2 3 , Che-Mai Chang 1 4 , Jafit Ting 1 , Min-Rou Lin 1 , Hsin-Ni Liao 1 , Yi-Chien Chou 1 , Chun-Yu Wei 1 5 , Hsin-Hui Chi 1 , Szu-Ying Ho 1 , Wei-Tzu Luo 1 , Cheng-Lin Tsai 1 , Ching-Hsuan Chao 1 , Lu-Chun Chen 1 , Tsung-Hsun Wu 1 , Wei-Chih Liu 1 , Quynh-Anh Nguyen 1 , Hui-Wen Chang 6 7 , Ching-Sheng **** 8 , Shiao-Ya Hong 9 , Jude Chu-Chun Wang 10 , Shih-Hsin Hsiao 10 11 , Wei-Chiao Chang 1 4 5 12 13 14
Affiliations
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 (ρlowPGS = -0.5, ρmediumPGS = -0.2, ρhighPGS = -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.
Keywords: COVID-19 vaccine responses; biomarker; genomics; host factors; polygenic effect.
. 2025 Sep 29:16:1622122.
doi: 10.3389/fimmu.2025.1622122. eCollection 2025. Identification of novel genetic biomarkers for ChAdOx1 nCoV-19 mediated immunogenicity
Wan-Hsuan Chou 1 2 3 , Che-Mai Chang 1 4 , Jafit Ting 1 , Min-Rou Lin 1 , Hsin-Ni Liao 1 , Yi-Chien Chou 1 , Chun-Yu Wei 1 5 , Hsin-Hui Chi 1 , Szu-Ying Ho 1 , Wei-Tzu Luo 1 , Cheng-Lin Tsai 1 , Ching-Hsuan Chao 1 , Lu-Chun Chen 1 , Tsung-Hsun Wu 1 , Wei-Chih Liu 1 , Quynh-Anh Nguyen 1 , Hui-Wen Chang 6 7 , Ching-Sheng **** 8 , Shiao-Ya Hong 9 , Jude Chu-Chun Wang 10 , Shih-Hsin Hsiao 10 11 , Wei-Chiao Chang 1 4 5 12 13 14
Affiliations
- PMID: 41089705
- PMCID: PMC12515888
- DOI: 10.3389/fimmu.2025.1622122
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 (ρlowPGS = -0.5, ρmediumPGS = -0.2, ρhighPGS = -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.
Keywords: COVID-19 vaccine responses; biomarker; genomics; host factors; polygenic effect.