High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics
DOI10.5281/zenodo.7357687Zenodo7357687MaRDI QIDQ6682223FDOQ6682223
Dataset published at Zenodo repository.
Tommy Carstensen, Sodiomon Sirima, Pontiano Kaleebu, Alexander Dilthey, Anna Rautanen, Alessandro Sette, Kathryn Auckland, Shabir Madhi, Adrian Hill, Cecilia Arlehamn, Manjinder Sandhu, Tom Parks, Martin O Pollard, Deepti Gurdasani, Samuel Neaves, Katie Ewer, Segun Fatumo, Alexander Mentzer, Nick Edwards, Ricardo da Silva Antunes, Nicolas Timpson, Hwaran Kim, Austin Crinklaw, Nezih Cereb, Alison Elliott, Katie Jeffery, Bjorn Peters, Allan Muhwezi, Debora Brandt, Rasmus Nielsen, Sarah Peacock, Emre Karakoc, Pandurangan Vijayanand, Sinu Paul, Kate Elliott, Gil McVean, Clare Cutland, Gaby Smits, Tara Mills, Amidou Diarra, Susan Wareing, Amanda Chong, Fiona van der Klis, Cristina Pomilla, Dennison Kizito
Publication date: 24 November 2022
Copyright license: Creative Commons Attribution 4.0 International
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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