High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics
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Mentzer, Alexander1
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Dilthey, Alexander2
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Pollard, Martin3
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Gurdasani, Deepti3
- Karakoc, Emre3
- Carstensen, Tommy3
- Muhwezi, Allan4
- Cutland, Clare5
- Diarra, Amidou6
- da Silva Antunes, Ricardo7
- Paul, Sinu7
- Smits, Gaby8
- Wareing, Susan9
- Kim, HwaRan10
- Pomilla, Cristina3
- Chong, Amanda1
- Brandt, Debora11
- Nielsen, Rasmus11
- Neaves, Samuel12
- Timpson, Nicolas12
- Crinklaw, Austin7
- Arlehamn, Cecilia7
- Rautanen, Anna1
- Kizito, Dennison4
- Parks, Tom13
- Auckland, Kathryn1
- Elliott, Kate1
- Mills, Tara1
- Ewer, Katie14
- Edwards, Nick14
- Fatumo, Segun4
- Peacock, Sarah15
- Jeffery, Katie9
- van der Klis, Fiona8
- Kaleebu, Pontiano4
- Vijayanand, Pandurangan7
- Peters, Bjorn7
- Sette, Alessandro7
- Cereb, Nezih10
- Sirima, Sodiomon6
- Madhi, Shabir5
- Elliott, Alison4
- McVean, Gil16
- Hill, Adrian14
- Sandhu, Manjinder17
- 1. Wellcome Centre for Human Genetics, University of Oxford, UK
- 2. Institute of Medical Microbiology and Hospital Hygiene, University Hospital of Düsseldorf, Heinrich Heine University Düsseldorf
- 3. Wellcome Sanger Institute, Hinxton, Cambridge, U
- 4. Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- 5. South African Medical Research Council Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand, Johannesburg, South Africa
- 6. Groupe de Recherche Action en Santé (GRAS) 06 BP 10248 Ouagadougou, Burkina Faso
- 7. Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, California, USA
- 8. National Institute for Public Health and the Environment, Bilthoven, The Netherlands
- 9. Microbiology Department, John Radcliffe Hospital, Oxford University NHS Foundation Trust, Oxford, UK
- 10. Histogenetics, New York, USA
- 11. Department of Integrative Biology, University of California at Berkeley, California, USA
- 12. Avon Longitudinal Study of Parents and Children at University of Bristol, Bristol, UK
- 13. Department of Infectious Disease, Imperial College London, UK
- 14. The Jenner Institute, University of Oxford, UK
- 15. Tissue Typing Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK
- 16. Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
- 17. Department of Epidemiology & Biostatistics, School of Public Health, Imperial College London, UK
Description
How human genetic variation contributes to vaccine immunogenicity and effectiveness is unclear, particularly in infants from Africa. We undertook genome-wide association analyses of eight vaccine antibody responses in 2,499 infants from three African countries and identified significant associations across the human leukocyte antigen (HLA) locus for five antigens spanning pertussis, diphtheria and hepatitis B vaccines. Using high-resolution HLA typing in 1,706 individuals from 11 African populations we constructed a continental imputation resource to fine-map signals of association across the class II HLA observing genetic variation explaining up to 10% of the observed variance in antibody responses. Using follicular helper T-cell assays, in silico binding, and immune cell eQTL datasets we find evidence of HLA-DRB1 expression correlating with serological response and inferred protection from pertussis following vaccination. This work improves our understanding of molecular mechanisms underlying HLA associations that should support vaccine design and development across Africa with wider global relevance.
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- Preprint: 10.1101/2022.11.24.22282715 (DOI)