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expert reaction to study looking at human genetics (HLA gene versions) and COVID-19 vaccine immune response and risk of breakthrough infection

A study published in Nature Medicine looks at human leukocyte antigen (HLA) alleles, COVID-19 vaccine immunogenicity, and risk of breakthrough infection.

This Roundup accompanied an SMC Briefing.


Prof Adam Finn, Professor of Paediatrics, University of Bristol, said:

“While the precise reasons why different individuals make widely different-sized immune responses to standard doses of vaccines are not fully understood, it’s long been known that this kind of diversity within the human species is one of the ways we ensure our survival.  Some of us are good at fighting off measles but not so good when it comes to malaria and so on.  That means that when a new infectious disease – like SARS CoV2 comes along – there’s much less risk of us going extinct – because at least some of us will have the right immunological equipment to combat the infection without dying of it in the process.

“This interesting study has been able to pinpoint one such genetically-programmed capability.  One particular version, that some people have, of the protein that presents one particular part of the Spike protein to our T cells makes them into anti-COVID “experts” that make stronger more protective responses which protect them better.

“The study has been conducted using rigorous methodology taking advantage of the biological samples and clinical information collected with consent during the studies done to evaluate the covid19 vaccine developed in Oxford.  The results appear convincing and robust.

“Why does this matter?  Well, it’s a small but important step in increasing our understanding of how vaccines work.  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.”



‘Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection’ by Alexander J. Mentzer et al. was published in Nature Medicine at 16:00 UK time on Thursday 13 October 2022.

DOI: 10.1038/s41591-022-02078-6



Declared interests

Prof Adam Finn is a member of JCVI and also does vaccine policy advisory work for WHO.  He is Chief Investigator of the Valneva vaccine clinical development programme in the UK.  He receives no remuneration for this work over and above his salary from the University of Bristol and has no personal or family financial or intellectual property assets related to this company or any other vaccine developer or manufacturer.

AF is an investigator in several COVID19 vaccine trials and studies including Oxford-AstraZeneca, Pfizer, Janssen and Valneva vaccines and several UK government-funded studies involving more than one vaccine.  He is U.K. Chief Investigator Sanofi COVID19 booster vaccine trial.  He is an advisor to the UK government as a member of JCVI.  He chairs the WHO Euro Technical Advisory Group of Experts and is a member of the WHO Special Advisory Group of Experts Working Group on COVID19 vaccines.  He undertakes consultancy work for several vaccine developers.  He receives no personal remuneration for any of this work, owns no IP or stocks and shares and is paid only in his role as Professor of Paediatrics at the University of Bristol.

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