Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection
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SARS-CoV-2 vaccine immunogenicity varies between individuals, and immune responses correlate with vaccine efficacy. Using data from 1,076 participants enrolled in ChAdOx1 nCov-19 vaccine efficacy trials in the United Kingdom, we find that inter-individual variation in normalised antibody responses against SARS-CoV-2 spike (S) and its receptor binding domain (RBD) at 28 days following first vaccination shows genome-wide significant association with major histocompatibility complex (MHC) class II alleles. The most statistically significant association with higher levels of anti-RBD antibody was HLA-DQB1*06 (P=3.2 x 10-9), which we replicate in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 alleles were less likely to experience PCR-confirmed breakthrough infection during the Wuhan and Alpha-variant waves compared to non-carriers (HR 0.63, 0.42-0.93, P=0.02). We identify a distinct S-derived peptide that is predicted to bind effectively to HLA-DQB1*06 compared to other equivalent alleles, and find evidence of increased spike-specific memory B-cell responses in ... (Show More)
Study Datasets 4 datasets.
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Imputed HLA alleles and variation. Imputation was carried out using the Multi-Ethnic HLA reference panel (version 1.0 2021) available on the Michigan imputation server
Phenotype and covariates
postQC genotype data from the Affymetrix AxiomTM HGCoV2 1 array in plink binary format. QC was carried out using PLINK v1.9
|Affymetrix AxiomTM HGCoV2 1||1192|
preQC genotype data from the Affymetrix AxiomTM HGCoV2 1 array in plink ped/map format
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