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

Publication date: Dec 31, 2024

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.

Concepts Keywords
Pcr Adult
Tailoring Aged
Taiwan Breakthrough Infections
Vaccine Case-Control Studies
COVID-19
COVID-19
COVID-19 Vaccines
COVID-19 Vaccines
Female
genetic polymorphisms
Genome-Wide Association Study
Humans
Male
Middle Aged
mRNA Vaccines
mRNA Vaccines
mRNA-based vaccines
Polymorphism, Single Nucleotide
Precision Medicine
SARS-CoV-2
Taiwan
Vaccination
Vaccine Efficacy
waning immunity

Semantics

Type Source Name
disease MESH COVID-19
disease IDO quality
disease MESH breakthrough infections
disease IDO cell
disease MESH Polygenic risk score

Original Article

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