High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics

Mentzer, A, Dilthey, A, Pollard, M, Gurdasani, D, Karakoc, E, Carstensen, T, Muhwezi, A, Cutland, C, Diarra, A, da Silva Antunes, R, Paul, S, Smits, G, Wareing, S, Kim, H, Pomilla, C, Chong, A, Brandt, D, Nielsen, R, Neaves, S, Timpson, N, Crinklaw, A, Arlehamn, C, Rautanen, A, Kizito, D, Parks, T, Auckland, K, Elliott, K, Mills, T, Ewer, K, Edwards, N, Fatumo, S, Peacock, S, Jeffery, K, van der Klis, F, Kaleebu, P, Vijayanand, P, Peters, B, Sette, A, Cereb, N, Sirima, S, Madhi, S, Elliott, A, McVean, G, Hill, A and Sandhu, M. 2022. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics. [Online]. Zenodo. Available from: https://doi.org/10.5281/zenodo.7357687

Mentzer, A, Dilthey, A, Pollard, M, Gurdasani, D, Karakoc, E, Carstensen, T, Muhwezi, A, Cutland, C, Diarra, A, da Silva Antunes, R, Paul, S, Smits, G, Wareing, S, Kim, H, Pomilla, C, Chong, A, Brandt, D, Nielsen, R, Neaves, S, Timpson, N, Crinklaw, A, Arlehamn, C, Rautanen, A, Kizito, D, Parks, T, Auckland, K, Elliott, K, Mills, T, Ewer, K, Edwards, N, Fatumo, S, Peacock, S, Jeffery, K, van der Klis, F, Kaleebu, P, Vijayanand, P, Peters, B, Sette, A, Cereb, N, Sirima, S, Madhi, S, Elliott, A, McVean, G, Hill, A and Sandhu, M. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics [Internet]. Zenodo; 2022. Available from: https://doi.org/10.5281/zenodo.7357687

Mentzer, A, Dilthey, A, Pollard, M, Gurdasani, D, Karakoc, E, Carstensen, T, Muhwezi, A, Cutland, C, Diarra, A, da Silva Antunes, R, Paul, S, Smits, G, Wareing, S, Kim, H, Pomilla, C, Chong, A, Brandt, D, Nielsen, R, Neaves, S, Timpson, N, Crinklaw, A, Arlehamn, C, Rautanen, A, Kizito, D, Parks, T, Auckland, K, Elliott, K, Mills, T, Ewer, K, Edwards, N, Fatumo, S, Peacock, S, Jeffery, K, van der Klis, F, Kaleebu, P, Vijayanand, P, Peters, B, Sette, A, Cereb, N, Sirima, S, Madhi, S, Elliott, A, McVean, G, Hill, A and Sandhu, M (2022). High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics. [Data Collection]. Zenodo. https://doi.org/10.5281/zenodo.7357687

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. This dataset contains GWAS summary statistics for eight vaccine antibody responses measured in 2,499 infants from three African counties: Uganda, South Africa and Burkina Faso.

Methods

Data capture method	Measurements and tests
Date (Date published in a 3rd party system)	24 November 2022
Language(s) of written materials	English

People & Groups

Data Creators	Mentzer, A, Dilthey, A, Pollard, M, Gurdasani, D, Karakoc, E, Carstensen, T, Muhwezi, A, Cutland, C, Diarra, A, da Silva Antunes, R, Paul, S, Smits, G, Wareing, S, Kim, H, Pomilla, C, Chong, A, Brandt, D, Nielsen, R, Neaves, S, Timpson, N, Crinklaw, A, Arlehamn, C, Rautanen, A, Kizito, D, Parks, T, Auckland, K, Elliott, K, Mills, T, Ewer, K, Edwards, N, Fatumo, S, Peacock, S, Jeffery, K, van der Klis, F, Kaleebu, P, Vijayanand, P, Peters, B, Sette, A, Cereb, N, Sirima, S, Madhi, S, Elliott, A, McVean, G, Hill, A and Sandhu, M
LSHTM Faculty/Department	MRC/UVRI and LSHTM Uganda Research Unit
Participating Institutions	London School of Hygiene & Tropical Medicine, London, United Kingdom