TY - JOUR
T1 - Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection
AU - Oxford COVID Vaccine Trial Genetics Study Team Group
AU - Mentzer, Alexander J.
AU - O’Connor, Daniel
AU - Bibi, Sagida
AU - Chelysheva, Irina
AU - Clutterbuck, Elizabeth A.
AU - Demissie, Tesfaye
AU - Dinesh, Tanya
AU - Edwards, Nick J.
AU - Felle, Sally
AU - Feng, Shuo
AU - Flaxman, Amy L.
AU - Karp-Tatham, Eleanor
AU - Li, Grace
AU - Liu, Xinxue
AU - Marchevsky, Natalie
AU - Godfrey, Leila
AU - Makinson, Rebecca
AU - Bull, Maireid B.
AU - Fowler, Jamie
AU - Alamad, Bana
AU - Malinauskas, Tomas
AU - Chong, Amanda Y.
AU - Sanders, Katherine
AU - Shaw, Robert H.
AU - Voysey, Merryn
AU - Cavey, Ana
AU - Minassian, Angela
AU - Stuart, Arabella
AU - Khozoee, Baktash
AU - Hanumunthadu, Brama
AU - Angus, Brian
AU - Smith, Catherine C.
AU - Turnbull, Iain
AU - Kwok, Jonathan
AU - Emary, Katherine R.W.
AU - Cifuentes, Liliana
AU - Ramasamy, Maheshi N.
AU - Cicconi, Paola
AU - Finn, Adam
AU - McGregor, Alastair C.
AU - Collins, Andrea
AU - Smith, Andrew
AU - Goodman, Anna L.
AU - Green, Christopher A.
AU - Duncan, Christopher J.A.
AU - Williams, Christopher J.A.
AU - Ferreira, Daniela
AU - Turner, David P.J.
AU - Thomson, Emma C.
AU - Hill, Helen
AU - Snape, Matthew D.
AU - Pollard, Andrew J.
AU - Lambe, Teresa
AU - Knight, Julian C.
PY - 2022/10/13
Y1 - 2022/10/13
N2 - 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.
AB - 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.
U2 - 10.1038/s41591-022-02078-6
DO - 10.1038/s41591-022-02078-6
M3 - Article
SN - 1078-8956
VL - 29
SP - 147
EP - 157
JO - Nature Medicine
JF - Nature Medicine
IS - 1
ER -
SDG 3 Good Health and Well-being