Mentzer, Alexander J; O'Connor, Daniel; Bibi, Sagida; Chelysheva, Irina; Clutterbuck, Elizabeth A; Demissie, Tesfaye; Dinesh, Tanya; Edwards, Nick J; Felle, Sally; Feng, Shuo; +20 more... Flaxman, Amy L; Karp-Tatham, Eleanor; Li, Grace; Liu, Xinxue; Marchevsky, Natalie; Godfrey, Leila; Makinson, Rebecca; Bull, Maireid B; Fowler, Jamie; Alamad, Bana; Malinauskas, Tomas; Chong, Amanda Y; Sanders, Katherine; Shaw, Robert H; Voysey, Merryn; Oxford COVID Vaccine Trial Genetics Study Team Group; Snape, Matthew D; Pollard, Andrew J; Lambe, Teresa; Knight, Julian C; (2023) Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection. Nature medicine, 29 (1). pp. 147-157. ISSN 1078-8956 DOI: https://doi.org/10.1038/s41591-022-02078-6
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Abstract
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-DQB1*06 (P = 3.2 × 10-9), which we replicated in 1,677 additional vaccinees. Individuals carrying HLA-DQB1*06 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-DQB1*06 compared to other similar alleles, and we found evidence of increased spike-specific memory B cell responses in HLA-DQB1*06 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.
Item Type | Article |
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PubMed ID | 36228659 |
Elements ID | 198317 |
Official URL | http://dx.doi.org/10.1038/s41591-022-02078-6 |
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Filename: Mentzer_etal_2022_Human-leukocyte-antigen-alleles-associate.pdf
Licence: Creative Commons: Attribution 4.0
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