Human leukocyte antigen variants associate with BNT162b2 mRNA vaccine response.
Journal
Communications medicine
ISSN: 2730-664X
Titre abrégé: Commun Med (Lond)
Pays: England
ID NLM: 9918250414506676
Informations de publication
Date de publication:
04 Apr 2024
04 Apr 2024
Historique:
received:
05
07
2023
accepted:
21
03
2024
medline:
5
4
2024
pubmed:
5
4
2024
entrez:
4
4
2024
Statut:
epublish
Résumé
Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1. We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above. Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels. These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination. It is known that people respond differently to vaccines. It has been proposed that differences in their genes might play a role. We studied the individual genetic makeup of 1351 people from Italy to see if there was a link between their genes and how well they responded to the BNT162b2 mRNA COVID-19 vaccine. We discovered certain genetic differences linked to higher levels of protection in those who got the vaccine. Our findings suggest that individual’s genetic characteristics play a role in vaccine response. A larger population involving diverse ethnic backgrounds will need to be studied to confirm the generalizability of these findings. Better understanding of this could facilitate improved vaccine designs against new SARS-CoV-2 variants.
Sections du résumé
BACKGROUND
BACKGROUND
Since the beginning of the anti-COVID-19 vaccination campaign, it has become evident that vaccinated subjects exhibit considerable inter-individual variability in the response to the vaccine that could be partly explained by host genetic factors. A recent study reported that the immune response elicited by the Oxford-AstraZeneca vaccine in individuals from the United Kingdom was influenced by a specific allele of the human leukocyte antigen gene HLA-DQB1.
METHODS
METHODS
We carried out a genome-wide association study to investigate the genetic determinants of the antibody response to the Pfizer-BioNTech vaccine in an Italian cohort of 1351 subjects recruited in three centers. Linear regressions between normalized antibody levels and genotypes of more than 7 million variants was performed, using sex, age, centers, days between vaccination boost and serological test, and five principal components as covariates. We also analyzed the association between normalized antibody levels and 204 HLA alleles, with the same covariates as above.
RESULTS
RESULTS
Our study confirms the involvement of the HLA locus and shows significant associations with variants in HLA-A, HLA-DQA1, and HLA-DQB1 genes. In particular, the HLA-A*03:01 allele is the most significantly associated with serum levels of anti-SARS-CoV-2 antibodies. Other alleles, from both major histocompatibility complex class I and II are significantly associated with antibody levels.
CONCLUSIONS
CONCLUSIONS
These results support the hypothesis that HLA genes modulate the response to Pfizer-BioNTech vaccine and highlight the need for genetic studies in diverse populations and for functional studies aimed to elucidate the relationship between HLA-A*03:01 and CD8+ cell response upon Pfizer-BioNTech vaccination.
It is known that people respond differently to vaccines. It has been proposed that differences in their genes might play a role. We studied the individual genetic makeup of 1351 people from Italy to see if there was a link between their genes and how well they responded to the BNT162b2 mRNA COVID-19 vaccine. We discovered certain genetic differences linked to higher levels of protection in those who got the vaccine. Our findings suggest that individual’s genetic characteristics play a role in vaccine response. A larger population involving diverse ethnic backgrounds will need to be studied to confirm the generalizability of these findings. Better understanding of this could facilitate improved vaccine designs against new SARS-CoV-2 variants.
Autres résumés
Type: plain-language-summary
(eng)
It is known that people respond differently to vaccines. It has been proposed that differences in their genes might play a role. We studied the individual genetic makeup of 1351 people from Italy to see if there was a link between their genes and how well they responded to the BNT162b2 mRNA COVID-19 vaccine. We discovered certain genetic differences linked to higher levels of protection in those who got the vaccine. Our findings suggest that individual’s genetic characteristics play a role in vaccine response. A larger population involving diverse ethnic backgrounds will need to be studied to confirm the generalizability of these findings. Better understanding of this could facilitate improved vaccine designs against new SARS-CoV-2 variants.
Identifiants
pubmed: 38575714
doi: 10.1038/s43856-024-00490-2
pii: 10.1038/s43856-024-00490-2
doi:
Types de publication
Journal Article
Langues
eng
Pagination
63Informations de copyright
© 2024. The Author(s).
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