The effect of HLA polymorphism on immune response to SARS‐CoV‐2 vaccination within an infection‐naïve, vulnerable population with end‐stage renal disease
Author(s)
Type
Journal Article
Abstract
HLA genes exhibit a high degree of polymorphism, contributing to genetic variability known to influence immune responses to infection. Here we investigate associations between HLA polymorphism and serological and T-lymphocyte responses to the BNT162b2 and ChAdOx1 SARS-CoV-2 vaccines within a population receiving maintenance haemodialysis (HD) for End-Stage Renal Disease (ESRD). Our primary objective was to identify HLA alleles associated with diminished serological and T-cellular responsiveness to vaccination. As a secondary objective, the associations between HLA type and COVID-19 disease outcomes were investigated using an independent ESRD cohort (n = 327). This aimed to determine if the alleles associated with poor vaccine response were also linked to unfavourable infection outcomes. In the main study, serum from 225 SARS-CoV-2 infection-naïve patients was HLA-typed using high-resolution Next Generation Sequencing, and serological titres were analysed for the presence of SARS-CoV-2 spike glycoprotein-specific antibodies after two doses of vaccination. A subset of patients (n = 33) was also tested for a T-lymphocyte response. Overall, 89% (n = 200) of patients seroconverted, but only 18% (n = 6) of the cellular response subgroup had a positive T-lymphocyte response. The HLA class II alleles DPB1*104:01, DRB1*04:03 and DRB1*14:04 and HLA class I alleles B*08:01 and B*18:01 were found to significantly correlate with seronegativity, and DQB1*06:01 correlated with serological responsiveness. We were unable to analyse the effect of HLA on disease outcome and T-lymphocyte response due to sample size limitations. Our results suggest pathways for further research and begin to elucidate the relationship between HLA polymorphism and immune responses in the vulnerable ESRD population.
Date Issued
2025-02-01
Date Acceptance
2025-02-04
Citation
HLA, 2025, 105 (2)
ISSN
2059-2302
Publisher
Wiley
Journal / Book Title
HLA
Volume
105
Issue
2
Copyright Statement
© 2025 The Author(s). HLA: Immune Response Genetics published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39991976
Subjects
Humans
Kidney Failure, Chronic
SARS-CoV-2
COVID-19
COVID-19 Vaccines
Female
Male
Middle Aged
Polymorphism, Genetic
Alleles
Aged
HLA Antigens
Vaccination
Renal Dialysis
Antibodies, Viral
Spike Glycoprotein, Coronavirus
BNT162 Vaccine
Vulnerable Populations
Adult
T-Lymphocytes
Publication Status
Published
Coverage Spatial
England
Article Number
e70076
Date Publish Online
2025-02-24