How could our genetics impact COVID-19 vaccine response?

ABSTRACT

Introduction

The 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 covered

This 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 opinion

Although 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.

KEYWORDS:

• COVID-19
• vaccine
• SARS-CoV-2
• immune response
• human genetics
• HLA
• GWAS

Article highlights

• SARS-CoV2 led to the most significant pandemic of modern times.

• Vaccination against SARS-Cov2 was one of the most successful coordinated public health initiatives ever undertaken.

• Human genetic variation has been consistently linked with variable immunogenicity against diverse SARS-CoV2 vaccines.

• Genetic variation has also been associated with risk of breakthrough infection following vaccination, and COVID-19 suceptibility.

• Variation across the HLA, particularly DRB1*13, DBQ1*06, and A*03 have been shown to be important in vaccine response and disease risk post-vaccination.

• Further understanding mechanisms underlying these HLA associations require continued data generation and sharing.

• Sharing of data from diverse populations may be particularly informative.

• Future approaches involving Artificial Intelligence could help use these associations to inform future vaccine design.

Declaration of interest

A Mentzer is a contributor to intellectual property licensed by Oxford University Innovation to AstraZeneca. The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.