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High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response
Alexander J Mentzer1,2, Alexander T Dilthey3,4,5, Martin Pollard6
1Centre for Human Genetics, University of Oxford, Oxford, UK. alexander.mentzer@ndm.ox.ac.uk.
Nature Medicine
|May 13, 2024
Summary
Human genetic variation, specifically human leukocyte antigen (HLA) genes, influences infant vaccine antibody responses. Understanding these genetic factors in diverse populations is key to improving vaccine effectiveness.
Area of Science:
- Immunogenetics
- Vaccinology
- Population Genetics
Background:
- Limited data exist on how human genetic variation impacts vaccine effectiveness in infants, particularly in populations of African ancestry.
- Understanding genetic influences on antibody response is crucial for optimizing vaccine efficacy across diverse populations.
Purpose of the Study:
- To investigate the association between human genetic variation, specifically human leukocyte antigen (HLA) genes, and vaccine antibody responses in African infants.
- To develop an imputation resource for HLA class II alleles to better understand antibody response variation.
- To explore the role of HLA-DRB1 expression in vaccine response and protection.
Main Methods:
- Genetic analyses of vaccine antibody responses in infant cohorts from Uganda, Burkina Faso, and South Africa.
- HLA typing of individuals from 11 African ancestry populations (1000 Genomes Project).
- Fine-mapping of HLA class II associations and analysis of immune cell expression quantitative trait loci (eQTLs).
Main Results:
- Identified significant associations between HLA and antibody responses for pertussis, diphtheria, and hepatitis B vaccines in African infants.
- Developed an HLA imputation resource explaining up to 10% of antibody response variance.
- Observed differences in pertussis antibody response genetic architecture between African and European ancestry cohorts, without differences in HLA peptide binding.
- Found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis.
Conclusions:
- Human leukocyte antigen (HLA) genetic variation significantly contributes to vaccine antibody responses in African infants.
- HLA-DRB1 expression may play a role in vaccine response and could be a target for improving vaccine design.
- Further research into population-specific genetic factors is essential for global vaccine development and efficacy.
