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Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection.
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; Snape, Matthew D; Pollard, Andrew J; Lambe, Teresa; Knight, Julian C.
Afiliação
  • Mentzer AJ; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. alexander.mentzer@ndm.ox.ac.uk.
  • O'Connor D; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Bibi S; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Chelysheva I; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Clutterbuck EA; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Demissie T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Dinesh T; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Edwards NJ; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Felle S; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Feng S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Flaxman AL; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Karp-Tatham E; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Li G; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Liu X; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Marchevsky N; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Godfrey L; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Makinson R; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Bull MB; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Fowler J; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Alamad B; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Malinauskas T; Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chong AY; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Sanders K; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Shaw RH; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Voysey M; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Snape MD; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Pollard AJ; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Lambe T; NIHR Oxford Biomedical Research Centre and Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
  • Knight JC; The Jenner Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Med ; 29(1): 147-157, 2023 01.
Article em En | MEDLINE | ID: mdl-36228659
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.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antígenos de Histocompatibilidade Classe II / Imunogenicidade da Vacina / Vacinas contra COVID-19 / COVID-19 / Infecções Irruptivas Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Antígenos de Histocompatibilidade Classe II / Imunogenicidade da Vacina / Vacinas contra COVID-19 / COVID-19 / Infecções Irruptivas Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article