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Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes

Author

Listed:
  • Junqing Xie

    (NDORMS, University of Oxford)

  • Beatriz Mothe

    (Hospital Universitari Germans Trias i Pujol)

  • Marta Alcalde Herraiz

    (NDORMS, University of Oxford)

  • Chunxiao Li

    (University of Cambridge)

  • Yu Xu

    (University of Cambridge
    University of Cambridge
    University of Cambridge)

  • Annika M. Jödicke

    (NDORMS, University of Oxford)

  • Yaqing Gao

    (University of Oxford)

  • Yunhe Wang

    (University of Oxford)

  • Shuo Feng

    (University of Oxford)

  • Jia Wei

    (University of Oxford)

  • Zhuoyao Chen

    (University of Oxford)

  • Shenda Hong

    (Peking University
    Peking University Health Science Center)

  • Yeda Wu

    (The University of Queensland)

  • Binbin Su

    (Chinese Academy of Medical Sciences/Peking Union Medical College)

  • Xiaoying Zheng

    (Chinese Academy of Medical Sciences/Peking Union Medical College)

  • Catherine Cohet

    (European Medicines Agency)

  • Raghib Ali

    (University of Cambridge
    New York University Abu Dhabi)

  • Nick Wareham

    (University of Cambridge)

  • Daniel Prieto Alhambra

    (NDORMS, University of Oxford
    Erasmus University Medical Centre)

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.

Suggested Citation

  • Junqing Xie & Beatriz Mothe & Marta Alcalde Herraiz & Chunxiao Li & Yu Xu & Annika M. Jödicke & Yaqing Gao & Yunhe Wang & Shuo Feng & Jia Wei & Zhuoyao Chen & Shenda Hong & Yeda Wu & Binbin Su & Xiaoy, 2024. "Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48339-5
    DOI: 10.1038/s41467-024-48339-5
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    1. Erola Pairo-Castineira & Konrad Rawlik & Andrew D. Bretherick & Ting Qi & Yang Wu & Isar Nassiri & Glenn A. McConkey & Marie Zechner & Lucija Klaric & Fiona Griffiths & Wilna Oosthuyzen & Athanasios K, 2023. "GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19," Nature, Nature, vol. 617(7962), pages 764-768, May.
    2. Junqing Xie & Shuo Feng & Xintong Li & Ester Gea-Mallorquí & Albert Prats-Uribe & Dani Prieto-Alhambra, 2022. "Comparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    3. Alexander Dilthey & Stephen Leslie & Loukas Moutsianas & Judong Shen & Charles Cox & Matthew R Nelson & Gil McVean, 2013. "Multi-Population Classical HLA Type Imputation," PLOS Computational Biology, Public Library of Science, vol. 9(2), pages 1-13, February.
    4. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    5. Deborah Cromer & Megan Steain & Arnold Reynaldi & Timothy E. Schlub & Shanchita R. Khan & Sarah C. Sasson & Stephen J. Kent & David S. Khoury & Miles P. Davenport, 2023. "Predicting vaccine effectiveness against severe COVID-19 over time and against variants: a meta-analysis," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    6. Erola Pairo-Castineira & Konrad Rawlik & Andrew D. Bretherick & Ting Qi & Yang Wu & Isar Nassiri & Glenn A. McConkey & Marie Zechner & Lucija Klaric & Fiona Griffiths & Wilna Oosthuyzen & Athanasios K, 2023. "Author Correction: GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19," Nature, Nature, vol. 619(7971), pages 61-61, July.
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    Cited by:

    1. Marta Alcalde-Herraiz & Martí Català & Albert Prats-Uribe & Roger Paredes & JunQing Xie & Daniel Prieto-Alhambra, 2024. "Genome-wide association studies of COVID-19 vaccine seroconversion and breakthrough outcomes in UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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