Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.

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Mentzer, Alexander J  ORCID logo
Bibi, Sagida 
Clutterbuck, Elizabeth A 

Severe acute respiratory syndrome coronavirus 2 (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 found that inter-individual variation in normalized antibody responses against SARS-CoV-2 spike and its receptor-binding domain (RBD) at 28 days after 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-DQB106 (P = 3.2 × 10-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB106 alleles were less likely to experience PCR-confirmed breakthrough infection during the ancestral SARS-CoV-2 virus and subsequent Alpha variant waves compared to non-carriers (hazard ratio = 0.63, 0.42-0.93, P = 0.02). We identified a distinct spike-derived peptide that is predicted to bind differentially to HLA-DQB106 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB106 carriers at 84 days after first vaccination. Our results demonstrate association of HLA type with Coronavirus Disease 2019 (COVID-19) vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.

Humans, Alleles, Antibodies, Viral, Breakthrough Infections, ChAdOx1 nCoV-19, COVID-19, COVID-19 Vaccines, Histocompatibility Antigens Class II, Immunogenicity, Vaccine, SARS-CoV-2, Vaccination
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Nat Med
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Springer Science and Business Media LLC