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Scientists Identify Genetic Link to COVID-19 Vaccine Effectiveness

Immunity against the SARS-CoV-2 virus from vaccination might be partially underpinned by genetic factors, according to scientists, who said the discovery could have implications for improving future vaccines.

A team at the University of Oxford reported results of a study that found people carrying an allele of a human leukocyte antigen (HLA) gene, HLA-DQB1*06, generated a higher antibody response following COVID-19 vaccination compared with those who did not have the allele.

Additionally, individuals carrying this gene were less likely to develop COVID after being vaccinated than those who did not have it.

The scientists claimed to have provided the first evidence that our genetic makeup and the protection offered by a COVID vaccine could be linked.

Julian Knight, professor of genomic medicine at the University's Wellcome Centre for Human Genetics, who led the investigation, said: "From this study we have evidence that our genetic makeup is one of the reasons why we may differ from each other in our immune response following COVID-19 vaccination."

The publishers said they were providing an unedited version of the manuscript to give early access to its findings, and that changes might be made before final publication.

Researchers Reviewed Trial Data

The early version of the study, published in Nature Magazine, initially analysed samples from 1190 participants enrolled in efficacy trials for ChAdOx1 nCov-19, the AstraZeneca/Oxford vaccine. They also examined DNA data from 1677 adults who had enrolled on the Com-COV research programme looking at second-dose options for people who received either the AstraZeneca/Oxford or Pfizer/BioNTech vaccines as a first dose, as well as DNA samples from children who had participated in clinical trials for ChAdOx1 nCov-19.

Results suggested that people carrying the HLA-DQB1*06 gene, which was present in two out of five of the participants, and thought to be broadly in line with the UK population as a whole, recorded higher antibody responses against the original 'wild' strain of SARS-CoV-2, and the subsequent Alpha variant, at 28 days following a first vaccine dose.

Dr Alexander Mentzer, group leader at the Wellcome Centre for Human Genetics, at the University of Oxford, and study first author, explained in a Science Media Centre briefing how the gene allele was present in 33.9% of participants reporting symptoms of COVID-19 with a positive swab test for SARS-CoV-2, but that "in the individuals that did not experience breakthrough infection, that were followed up in this study, a large proportion, 45.6%, carried HLA-DQB1*06".

Discovery Could Shape Future Vaccine Development

Dr Mentzer said: "We hope that our findings will help us improve vaccines for the future, so they not only stop us developing severe disease, but also keep us symptom-free for as long as possible."

Adam Finn, professor of paediatrics at the University of Bristol, described the study as "interesting", and "a small but important step in increasing our understanding of how vaccines work".

He told the Science Media Centre: "Ultimately it could lead to vaccines designed to give stronger protection to people whose responses might otherwise be too weak.  One day, rather further into the future, there might be different vaccines designed for different people classified by the genetics of their immune systems, either at the individual level or even at the level of whole communities in different locations around the world."

Prof Julian Knight declared his interests as: "I am employed by the University of Oxford and Merton College; my role includes work as an honorary consultant physician at Oxford University Hospitals NHS Trust and I am research director at the Central and South NHS Genomic Medicine Service Alliance. Grant and research funding relating to this work includes the Wellcome Trust, NIHR Oxford Biomedical Research Centre, UK Research and Innovation. Dr Alexander Mentzer confirmed he had no interests to declare. Among interests declared by Prof Adam Finn were membership of the JCVI, vaccine policy advisory work for WHO, and a role as chief investigator of the Valneva vaccine clinical development programme in the UK for which he receives no remuneration above his salary from the University of Bristol.

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