@article{Mentzer_A-2022_106679,
title = {Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection},
author = {Mentzer, A. and O’Connor, D. and Bibi, S. and Chelysheva, I. and Clutterbuck, E. and Demissie, T. and Dinesh, T. and Edwards, N. and Felle, S. and Feng, S. and Flaxman, A. and Karp-Tatham, E. and Li, G. and Liu, X. and Marchevsky, N. and Godfrey, L. and Makinson, R. and Bull, M. and Fowler, J. and Alamad, B. and Malinauskas, T. and Chong, A. and Sanders, K. and Shaw, R. and Voysey, M. and Cavey, A. and Minassian, A. and Stuart, A. and Khozoee, B. and Hanumunthadu, B. and Angus, B. and Smith, C. and Turnbull, I. and Kwok, J. and Emary, K. and Cifuentes, L. and Ramasamy, M. and Cicconi, P. and Finn, A. and McGregor, A. and Collins, A. and Smith, A. and Goodman, A. and Green, C. and Duncan, C. and Williams, C. and Ferreira, D. and Turner, D. and Thomson, E. and Hill, H. and Pollock, K. and Toshner, M. and Lillie, P. and Heath, P. and Lazarus, R. and Sutherland, R. and Payne, R. and Faust, S. and Darton, T. and Libri, V. and Anslow, R. and Provtsgaard-Morys, S. and Hart, T. and Beveridge, A. and Adlou, S. and Snape, M. and Pollard, A. and Lambe, T. and Knight, J.},
month = {oct},
year = {2022},
abstract = {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 × 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 ancestral SARS-CoV-2 virus and subsequent Alpha-variant waves compared with non-carriers (HR 0.63, 0.42–0.93, P = 0.02). We identify a distinct S-derived peptide that is predicted to bind differentially to HLA-DQB1*06 compared with other similar alleles, and find evidence of increased spike-specific memory B-cell responses in HLA-DQB1*06 carriers at 84 days following first vaccination. Our results demonstrate association of HLA type with COVID-19 vaccine antibody response and risk of breakthrough infection, with implications for future vaccine design and implementation.},
pages = {147-157},
volume = {29},
issue = {1},
journal = {Nature Medicine},
publisher = {Springer Nature},
url = {https://doi.org/10.1038/s41591-022-02078-6},
}
