The Effect of <scp>HLA</scp> Polymorphism on Immune Response to <scp>SARS</scp>‐<scp>CoV</scp>‐2 Vaccination Within an Infection‐Naïve, Vulnerable Population With End‐Stage Renal Disease

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.