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

## TL;DR

This study identifies genetic factors influencing immune responses to a DNA-based COVID-19 vaccine in a Taiwanese population, highlighting potential biomarkers for personalized vaccination strategies.

## Contribution

The study provides novel genetic biomarkers for vaccine responses in an Asian population, revealing synergistic host effects with age and sex.

## Key findings

- 501 genetic associations linked to vaccine responses were identified, enriched in lipid metabolism and immune signaling pathways.
- Genetic variants interact with age and sex to influence antibody levels after vaccination.
- Lower polygenic scores correlate with stronger age-related declines in antibody response.

## Abstract

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.

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.