Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes
Xie, Junqing (University of Oxford)
Mothe, Beatriz (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Alcalde-Herraiz, Marta (University of Oxford)
Li, Chunxiao (University of Cambridge)
Xu, Yu (University of Cambridge)
Jödicke, Annika (University of Oxford)
Gao, Yaqing (University of Oxford)
Wang, Yunhe (University of Oxford)
Feng, Shuo (University of Oxford)
Wei, Jia (University of Oxford)
Chen, Zhuoyao (University of Oxford)
Hong, Shenda (Peking University)
Wu, Yeda (The University of Queensland)
Su, Binbin (Chinese Academy of Medical Sciences/Peking Union Medical College)
Zheng, Xiaoying (Chinese Academy of Medical Sciences/Peking Union Medical College)
Cohet, Catherine (Real-World Evidence Workstream. Data Analytics and Methods Task Force. European Medicines Agency)
Ali, Raghib (University of Cambridge)
Wareham, Nicholas (University of Cambridge)
Prieto-Alhambra, Daniel (University of Oxford)

Date:	2024
Abstract:	The rapid global distribution of COVID-19 vaccines, with over a billion doses administered, has been unprecedented. However, in comparison to most identified clinical determinants, the implications of individual genetic factors on antibody responses post-COVID-19 vaccination for breakthrough outcomes remain elusive. Here, we conducted a population-based study including 357,806 vaccinated participants with high-resolution HLA genotyping data, and a subset of 175,000 with antibody serology test results. We confirmed prior findings that single nucleotide polymorphisms associated with antibody response are predominantly located in the Major Histocompatibility Complex region, with the expansive HLA-DQB1*06 gene alleles linked to improved antibody responses. However, our results did not support the claim that this mutation alone can significantly reduce COVID-19 risk in the general population. In addition, we discovered and validated six HLA alleles (A*03:01, C*16:01, DQA1*01:02, DQA1*01:01, DRB3*01:01, and DPB1*10:01) that independently influence antibody responses and demonstrated a combined effect across HLA genes on the risk of breakthrough COVID-19 outcomes. Lastly, we estimated that COVID-19 vaccine-induced antibody positivity provides approximately 20% protection against infection and 50% protection against severity. These findings have immediate implications for functional studies on HLA molecules and can inform future personalised vaccination strategies.
Note:	Altres ajuts: Senior Research Fellowship (Grant number SRF-2018-11-ST2-004)
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Nature communications, Vol. 15, Núm. 1 (May 2024) , ISSN 2041-1723

DOI: 10.1038/s41467-024-48339-5
PMID: 38740772

11 p, 2.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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