Genomic insights into mRNA COVID-19 vaccines efficacy: Linking genetic polymorphisms to waning immunity

被引:1
|
作者
Hsieh, Min-Jia [1 ]
Tsai, Ping-Hsing [2 ]
Chiang, Pin-Hsuan [3 ]
Kao, Zih-Kai [4 ]
Zhuang, Zi-Qing [3 ]
Hsieh, Ai-Ru [5 ]
Ho, Hsiang-Ling [6 ,7 ]
Chiou, Shih-Hwa [2 ,8 ]
Liang, Kung-Hao [2 ,9 ,10 ,11 ]
Chen, Yu-Chun [1 ,3 ,8 ,12 ]
机构
[1] Taipei Vet Gen Hosp, Dept Family Med, Taipei, Taiwan
[2] Taipei Vet Gen Hosp, Dept Med Res, 201,Sec 2,Shipai Rd, Taipei 11217, Taiwan
[3] Taipei Vet Gen Hosp, Big Data Ctr, Taipei, Taiwan
[4] Taipei Vet Gen Hosp, Dept Informat Management, Taipei, Taiwan
[5] Tamkang Univ, Dept Stat, New Taipei, Taiwan
[6] Taipei Vet Gen Hosp, Dept Pathol & Lab Med, Taipei, Taiwan
[7] Natl Yang Ming Chiao Tung Univ, Dept Biotechnol & Lab Sci Med, Taipei, Taiwan
[8] Natl Yang Ming Chiao Tung Univ, Sch Med, Taipei, Taiwan
[9] Taipei Vet Gen Hosp, Biosafety Level Lab 3, Taipei, Taiwan
[10] Natl Yang Ming Chiao Tung Univ, Inst Biomed Informat, Taipei, Taiwan
[11] Natl Yang Ming Chiao Tung Univ, Inst Food Safety & Hlth Risk Assessment, Taipei, Taiwan
[12] Taipei Vet Gen Hosp, Dept Family Med, Yuli Branch, Hualien, Taiwan
关键词
COVID-19; mRNA-based vaccines; waning immunity; genetic polymorphisms; long-term memory CD8+T cells; RESPONSES;
D O I
10.1080/21645515.2024.2399382
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.
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页数:12
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