| Title: |
Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection |
| Authors: |
Mentzer, Alexander J.; O’connor, Daniel; Bibi, Sagida; Chelysheva, Irina; Clutterbuck, Elizabeth A.; Demissie, Tesfaye; Dinesh, Tanya; Edwards, Nick J.; Felle, Sally; Feng, Shuo; 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; Cavey, Ana; Minassian, Angela; Stuart, Arabella; Khozoee, Baktash; Hanumunthadu, Brama; Angus, Brian; Smith, Catherine C.; Turnbull, Iain; Kwok, Jonathan; Emary, Katherine R. W.; Cifuentes, Liliana; Ramasamy, Maheshi N.; Cicconi, Paola; Finn, Adam; Mcgregor, Alastair C.; Collins, Andrea M.; Smith, Andrew; Goodman, Anna L.; Green, Christopher A.; Duncan, Christopher J. A.; Williams, Christopher J. A.; Ferreira, Daniela M.; Turner, David P. J.; Thomson, Emma C.; Faust, Saul N. |
| Publication Year: |
2023 |
| Collection: |
University of Southampton: e-Prints Soton |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://eprints.soton.ac.uk/476011/1/s41591_022_02078_6.pdf; Mentzer, Alexander J., O’connor, Daniel, Bibi, Sagida, Chelysheva, Irina, Clutterbuck, Elizabeth A. and Demissie, Tesfaye , Oxford COVID Vaccine Trial Genetics Study Team Group (2023) Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection. Nature Medicine, 29 (1), 147-157. (doi:10.1038/s41591-022-02078-6 ). |
| Availability: |
https://eprints.soton.ac.uk/476011/; https://eprints.soton.ac.uk/476011/1/s41591_022_02078_6.pdf |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.A9F95547 |
| Database: |
BASE |