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

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

    Nat Commun


    . 2024 May 13;15(1):4031.
    doi: 10.1038/s41467-024-48339-5. Relationship between HLA genetic variations, COVID-19 vaccine antibody response, and risk of breakthrough outcomes

    Junqing Xie 1 , Beatriz Mothe 2 , Marta Alcalde Herraiz 1 , Chunxiao Li 3 , Yu Xu 4 5 6 , Annika M Jödicke 1 , Yaqing Gao 7 , Yunhe Wang 7 , Shuo Feng 8 , Jia Wei 9 , Zhuoyao Chen 10 , Shenda Hong 11 12 , Yeda Wu 13 , Binbin Su 14 , Xiaoying Zheng 14 , Catherine Cohet 15 , Raghib Ali 3 16 , Nick Wareham 3 , Daniel Prieto Alhambra 17 18



    AffiliationsAbstract

    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.


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