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

tetano

Editor, Senior Moderator
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[SUP] 1 2 3 [/SUP], Che-Mai Chang[SUP] 1 4 [/SUP], Jafit Ting[SUP] 1 [/SUP], Min-Rou Lin[SUP] 1 [/SUP], Hsin-Ni Liao[SUP] 1 [/SUP], Yi-Chien Chou[SUP] 1 [/SUP], Chun-Yu Wei[SUP] 1 5 [/SUP], Hsin-Hui Chi[SUP] 1 [/SUP], Szu-Ying Ho[SUP] 1 [/SUP], Wei-Tzu Luo[SUP] 1 [/SUP], Cheng-Lin Tsai[SUP] 1 [/SUP], Ching-Hsuan Chao[SUP] 1 [/SUP], Lu-Chun Chen[SUP] 1 [/SUP], Tsung-Hsun Wu[SUP] 1 [/SUP], Wei-Chih Liu[SUP] 1 [/SUP], Quynh-Anh Nguyen[SUP] 1 [/SUP], Hui-Wen Chang[SUP] 6 7 [/SUP], Ching-Sheng Hung[SUP] 8 [/SUP], Shiao-Ya Hong[SUP] 9 [/SUP], Jude Chu-Chun Wang[SUP] 10 [/SUP], Shih-Hsin Hsiao[SUP] 10 11 [/SUP], Wei-Chiao Chang[SUP] 1 4 5 12 13 14 [/SUP]



Affiliations
Abstract

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[SUB]lowPGS[/SUB] = -0.5, ρ[SUB]mediumPGS[/SUB] = -0.2, ρ[SUB]highPGS[/SUB] = -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.

 
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