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IntroductionThe COVID-19 pandemic, caused by the SARS-CoV-2 virus, has posed unprecedented global health challenges since its emergence in December 2019. The rapid availability of vaccines has been estimated to save millions of lives, but there is variation in how individuals respond to vaccines, influencing their effectiveness at an individual, and population level.Areas coveredThis review focuses on human genetic factors influencing the immune response and effectiveness of vaccines, highlighting the importance of associations across the HLA locus. Genome-Wide Association Studies (GWAS) and other genetic association analyses have identified statistically significant associations between specific HLA alleles including HLA-DRB1*13, DBQ1*06, and A*03 impacting antibody responses and the risk of breakthrough infections post-vaccination. Relationships between these associations and potential mechanisms and links with risks of natural infection or disease are explored, and this review concludes by emphasizing how understanding the mechanisms of these genetic determinants may inform the development of tailored vaccination strategies.Expert opinionAlthough complex, we believe these findings from the SARS-CoV2 pandemic offer a unique opportunity to understand the relationships between HLA and infection and vaccine response, with a goal of optimizing individual protection against COVID-19 in the ongoing pandemic, and possibly influencing wider vaccine development in the future.

Original publication




Journal article


Expert review of clinical immunology

Publication Date



1 - 13


Centre for Human Genetics, University of Oxford, Oxford, UK.