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

Mentzer, A. J. et al. (2023) Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection. Nature Medicine, 29(1), pp. 147-157. (doi: 10.1038/s41591-022-02078-6) (PMID:36228659) (PMCID:PMC9873562)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Smith, Professor Andrew
• Authors: Mentzer, A. J., O’Connor, D., Bibi, S., Chelysheva, I., Clutterbuck, E. A., Demissie, T., Dinesh, T., Edwards, N. J., Felle, S., Feng, S., Flaxman, A. L., Karp-Tatham, E., Li, G., Liu, X., Marchevsky, N., Godfrey, L., Makinson, R., Bull, M. B., Fowler, J., Alamad, B., Malinauskas, T., Chong, A. Y., Sanders, K., Shaw, R. H., Voysey, M., Cavey, A., Minassian, A., Stuart, A., Khozoee, B., Hanumunthadu, B., Angus, B., Smith, C. C., Turnbull, I., Kwok, J., Emary, K. R. W., Cifuentes, L., Ramasamy, M. N., Cicconi, P., Finn, A., McGregor, A. C., Collins, A. M., Smith, A., Goodman, A. L., Green, C. A., Duncan, C. J. A., Williams, C. J. A., Ferreira, D. M., Turner, D. P. J., Thomson, E. C., Hill, H., Pollock, K., Toshner, M., Lillie, P. J., Heath, P., Lazarus, R., Sutherland, R. K., Payne, R. O., Faust, S. N., Darton, T., Libri, V., Anslow, R., Provtsgaard-Morys, S., Hart, T., Beveridge, A., Adlou, S., Snape, M. D., Pollard, A. J., Lambe, T., and Knight, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
• Journal Name: Nature Medicine
• Publisher: Nature Research
• ISSN: 1078-8956
• ISSN (Online): 1546-170X
• Published Online: 13 October 2022
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Nature Medicine 29(1): 147-157
• Publisher Policy: Reproduced under a Creative Commons License