High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response.

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
13 May 2024

Historique:

received: 08 02 2023

accepted: 25 03 2024

medline: 14 5 2024

pubmed: 14 5 2024

entrez: 13 5 2024

Statut: aheadofprint

Résumé

How human genetic variation contributes to vaccine effectiveness in infants is unclear, and data are limited on these relationships in populations with African ancestries. We undertook genetic analyses of vaccine antibody responses in infants from Uganda (n = 1391), Burkina Faso (n = 353) and South Africa (n = 755), identifying associations between human leukocyte antigen (HLA) and antibody response for five of eight tested antigens spanning pertussis, diphtheria and hepatitis B vaccines. In addition, through HLA typing 1,702 individuals from 11 populations of African ancestry derived predominantly from the 1000 Genomes Project, we constructed an imputation resource, fine-mapping class II HLA-DR and DQ associations explaining up to 10% of antibody response variance in our infant cohorts. We observed differences in the genetic architecture of pertussis antibody response between the cohorts with African ancestries and an independent cohort with European ancestry, but found no in silico evidence of differences in HLA peptide binding affinity or breadth. Using immune cell expression quantitative trait loci datasets derived from African-ancestry samples from the 1000 Genomes Project, we found evidence of differential HLA-DRB1 expression correlating with inferred protection from pertussis following vaccination. This work suggests that HLA-DRB1 expression may play a role in vaccine response and should be considered alongside peptide selection to improve vaccine design.

Identifiants

DOI: 10.1038/s41591-024-02944-5 PMID: 38740997

pubmed: 38740997

doi: 10.1038/s41591-024-02944-5

pii: 10.1038/s41591-024-02944-5

doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Subventions

Organisme : Academy of Medical Sciences

ID : SGL024\1096

Pays : United Kingdom

Informations de copyright

Références

Ozawa, S. et al. Return on investment from childhood immunization in low- and middle-income countries, 2011–20. Health Aff. https://doi.org/10.1377/hlthaff.2015.1086 (2017).

Pollard, A. J. & Bijker, E. M. A guide to vaccinology: from basic principles to new developments. Nat. Rev. Immunol. 21, 83–100 (2020).

pubmed: 33353987 pmcid: 7754704 doi: 10.1038/s41577-020-00479-7

Cherry, J. D. Epidemic pertussis in 2012–the resurgence of a vaccine-preventable disease. N. Engl. J. Med. 367, 785–787 (2012).

pubmed: 22894554 doi: 10.1056/NEJMp1209051

Cherry, J. D. The 112-year odyssey of pertussis and pertussis vaccines–mistakes made and implications for the future. J. Pediatr. Infect. Dis. Soc. 8, 334–341 (2019).

doi: 10.1093/jpids/piz005

Schrager, L. K., Vekemens, J., Drager, N., Lewinsohn, D. M. & Olesen, O. F. The status of tuberculosis vaccine development. Lancet Infect. Dis. 20, e28–e37 (2020).

pubmed: 32014117 doi: 10.1016/S1473-3099(19)30625-5

Laurens, M. B. The promise of a malaria vaccine—are we closer? Annu. Rev. Microbiol. 72, 273–292 (2018).

pubmed: 30200856 doi: 10.1146/annurev-micro-090817-062427

Burton, D. R. Advancing an HIV vaccine; advancing vaccinology. Nat. Rev. Immunol. 19, 77–78 (2019).

pubmed: 30560910 pmcid: 6425752 doi: 10.1038/s41577-018-0103-6

Keehner, J. et al. Resurgence of SARS-CoV-2 infection in a highly vaccinated health system workforce. https://doi.org/10.1056/NEJMc2112981 (2021).

Plotkin, S. A. Correlates of protection induced by vaccination. Clin. Vaccin. Immunol. 17, 1055–1065 (2010).

doi: 10.1128/CVI.00131-10

Kwok, A. J., Mentzer, A. & Knight, J. C. Host genetics and infectious disease: new tools, insights and translational opportunities. Nat. Rev. Genet. 22, 137–153 (2020).

pubmed: 33277640 pmcid: 7716795 doi: 10.1038/s41576-020-00297-6

O’Connor, D. et al. Common genetic variations associated with the persistence of immunity following childhood immunization. Cell Rep. 27, 3241–3253 (2019).

pubmed: 31189108 doi: 10.1016/j.celrep.2019.05.053

Ovsyannikova, I. G. et al. A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses. PLoS ONE 12, e0171261 (2017).

pubmed: 28158231 pmcid: 5291460 doi: 10.1371/journal.pone.0171261

Trowsdale, J. & Knight, J. C. Major histocompatibility complex genomics and human disease. Annu Rev. Genomics Hum. Genet. 14, 301–323 (2013).

pubmed: 23875801 pmcid: 4426292 doi: 10.1146/annurev-genom-091212-153455

Chapman, S. J. & Hill, A. V. S. Human genetic susceptibility to infectious disease. Nat. Rev. Genet. 13, 175–188 (2012).

pubmed: 22310894 doi: 10.1038/nrg3114

Blackwell, J. M., Jamieson, S. E. & Burgner, D. HLA and infectious diseases. Clin. Microbiol. Rev. 22, 370–385 (2009).

pubmed: 19366919 pmcid: 2668228 doi: 10.1128/CMR.00048-08

Mentzer, A. J. et al. Human leukocyte antigen alleles associate with COVID-19 vaccine immunogenicity and risk of breakthrough infection. Nat. Med. https://doi.org/10.1038/S41591-022-02078-6 (2022).

doi: 10.1038/S41591-022-02078-6 pubmed: 36228659 pmcid: 9873562

Moutsianas, L. et al. Class II HLA interactions modulate genetic risk for multiple sclerosis. Nat. Genet. 47, 1107–1113 (2015).

Goyette, P. et al. High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat. Genet. 47, 172–179 (2015).

pubmed: 25559196 pmcid: 4310771 doi: 10.1038/ng.3176

Ramsuran, V. et al. Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells. Science https://doi.org/10.1126/science.aam8825 (2018).

doi: 10.1126/science.aam8825 pubmed: 29302013 pmcid: 5933048

Gurdasani, D. et al. Uganda genome resource enables insights into population history and genomic discovery in Africa. Cell 179, 984–1002 (2019).

pubmed: 31675503 pmcid: 7202134 doi: 10.1016/j.cell.2019.10.004

Dilthey, A. et al. Multi-population classical HLA type imputation. PLoS Comput. Biol. 9, e1002877 (2013).

pubmed: 23459081 pmcid: 3572961 doi: 10.1371/journal.pcbi.1002877

Luo, Y. et al. A high-resolution HLA reference panel capturing global population diversity enables multi-ancestry fine-mapping in HIV host response. Nat. Genet. 53, 1504–1516 (2021).

pubmed: 34611364 pmcid: 8959399 doi: 10.1038/s41588-021-00935-7

McMahon, G., Ring, S. M., Davey-Smith, G. & Timpson, N. J. Genome-wide association study identifies SNPs in the MHC class II loci that are associated with self-reported history of whooping cough. Hum. Mol. Genet. 24, 5930–5939 (2015).

pubmed: 26231221 pmcid: 4581602 doi: 10.1093/hmg/ddv293

Dan, J. M. et al. A cytokine-independent approach to identify antigen-specific human germinal center T follicular helper cells and rare antigen-specific CD4

pubmed: 27342848 doi: 10.4049/jimmunol.1600318

Schmiedel, B. J. et al. Impact of genetic polymorphisms on human immune cell gene expression. Cell 175, 1701–1715 (2018).

pubmed: 30449622 pmcid: 6289654 doi: 10.1016/j.cell.2018.10.022

Orrù, V. et al. Complex genetic signatures in immune cells underlie autoimmunity and inform therapy. Nat. Genet. 52, 1036–1045 (2020).

pubmed: 32929287 pmcid: 8517961

Zhang, Z. et al. Host genetic determinants of hepatitis B virus infection. Front. Genet. 10, 696 (2019).

pubmed: 31475028 pmcid: 6702792 doi: 10.3389/fgene.2019.00696

Akcay, I. M., Katrinli, S., Ozdil, K., Doganay, G. D. & Doganay, L. Host genetic factors affecting hepatitis B infection outcomes: Insights from genome-wide association studies. World J. Gastroenterol. 24, 3347–3360 (2018).

pubmed: 30122875 pmcid: 6092584 doi: 10.3748/wjg.v24.i30.3347

Haralambieva, I. H. et al. Genome-wide associations of CD46 and IFI44L genetic variants with neutralizing antibody response to measles vaccine. Hum. Genet 136, 421–435 (2017).

pubmed: 28289848 pmcid: 5433429 doi: 10.1007/s00439-017-1768-9

Prentice, H. A. et al. HLA class II genes modulate vaccine-induced antibody responses to affect HIV-1 acquisition. Sci. Transl. Med. 7, 296ra112 (2015).

pubmed: 26180102 pmcid: 4911012 doi: 10.1126/scitranslmed.aab4005

Sveinbjornsson, G. et al. HLA class II sequence variants influence tuberculosis risk in populations of European ancestry. Nat. Genet. 48, 318–322 (2016).

pubmed: 26829749 pmcid: 5081101 doi: 10.1038/ng.3498

Kamatani, Y. et al. A genome-wide association study identifies variants in the HLA-DP locus associated with chronic hepatitis B in Asians. Nat. Genet. 41, 591–595 (2009).

pubmed: 19349983 doi: 10.1038/ng.348

Nishida, N. et al. Genome-wide association study confirming association of HLA-DP with protection against chronic hepatitis B and viral clearance in Japanese and Korean. PLoS ONE 7, e39175 (2012).

pubmed: 22737229 pmcid: 3380898 doi: 10.1371/journal.pone.0039175

Low, J. S. et al. Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2. Science 372, 1336–1341 (2021).

pubmed: 34006597 doi: 10.1126/science.abg8985

Vince, N. et al. HLA-C level is regulated by a polymorphic Oct1 binding site in the HLA-C promoter region. Am. J. Hum. Genet. 99, 1353–1358 (2016).

pubmed: 27817866 pmcid: 5142108 doi: 10.1016/j.ajhg.2016.09.023

Gutierrez-Arcelus, M. et al. Allele-specific expression changes dynamically during T cell activation in HLA and other autoimmune loci. Nat. Genet. 52, 247–253 (2020).

pubmed: 32066938 pmcid: 7135372 doi: 10.1038/s41588-020-0579-4

Moore, S. E. et al. Effect of month of vaccine administration on antibody responses in The Gambia and Pakistan. Trop. Med. Int. Health 11, 1529–1541 (2006).

pubmed: 17002727 doi: 10.1111/j.1365-3156.2006.01700.x

Fang, J. W. S., Lai, C. L., Chung, H. T., Wu, P. C. & Lau, J. Y. N. Female children respond to recombinant hepatitis b vaccine with a higher titre than male. J. Trop. Pediatr. 40, 104–107 (1994).

pubmed: 8015023 doi: 10.1093/tropej/40.2.104

Kooijman, S. et al. Novel identified aluminum hydroxide-induced pathways prove monocyte activation and pro-inflammatory preparedness. J. Proteom. 175, 144–155 (2018).

doi: 10.1016/j.jprot.2017.12.021

Becker, R. A. & Wilks, A. R. Maps in S. AT&T Bell Laboratories Statistics Research Report [93.2] http://ect.bell-labs.com/sl/doc/93.2.ps (1993).

International HapMap 3 Consortium et al. Integrating common and rare genetic variation in diverse human populations. Nature 467, 52–58 (2010).

Webb, E. L. et al. Effect of single-dose anthelmintic treatment during pregnancy on an infant’s response to immunisation and on susceptibility to infectious diseases in infancy: a randomised, double-blind, placebo-controlled trial. Lancet 377, 52–62 (2011).

pubmed: 21176950 pmcid: 3018567 doi: 10.1016/S0140-6736(10)61457-2

Nash, S. et al. The impact of prenatal exposure to parasitic infections and to anthelminthic treatment on antibody responses to routine immunisations given in infancy: secondary analysis of a randomised controlled trial. PLoS Negl. Trop. Dis. 11, e0005213 (2017).

pubmed: 28178298 pmcid: 5298230 doi: 10.1371/journal.pntd.0005213

Nunes, M. C. et al. Duration of infant protection against influenza illness conferred by maternal immunization: secondary analysis of a randomized clinical trial. JAMA Pediatr. 170, 840–847 (2016).

pubmed: 27380464 doi: 10.1001/jamapediatrics.2016.0921

Madhi, S. A. et al. Influenza vaccination of pregnant women and protection of their infants. N. Engl. J. Med. 371, 918–931 (2014).

pubmed: 25184864 doi: 10.1056/NEJMoa1401480

Bliss, C. M. et al. Viral vector malaria vaccines induce high-level T cell and antibody responses in West African children and infants. Mol. Ther. 25, 547–559 (2017).

pubmed: 28153101 pmcid: 5368405 doi: 10.1016/j.ymthe.2016.11.003

Tiono, A. B. et al. First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5–17 months old infants and children. PLoS ONE 13, e0208328 (2018).

pubmed: 30540808 pmcid: 6291132 doi: 10.1371/journal.pone.0208328

Boyd, A. et al. Cohort profile: the ‘children of the 90s’—The index offspring of the Avon Longitudinal Study of Parents and Children. Int. J. Epidemiol. 42, 111–127 (2013).

pubmed: 22507743 doi: 10.1093/ije/dys064

Fraser, A. et al. Cohort profile: The Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int. J. Epidemiol. 42, 97–110 (2013).

pubmed: 22507742 doi: 10.1093/ije/dys066

Cereb, N., Kim, H. R., Ryu, J. & Yang, S. Y. Advances in DNA sequencing technologies for high resolution HLA typing. Hum. Immunol. 76, 923–927 (2015).

pubmed: 26423536 doi: 10.1016/j.humimm.2015.09.015

Mack, S. J. et al. Common and well-documented HLA alleles: 2012 update to the CWD catalogue. Tissue Antigens 81, 194–203 (2013).

pubmed: 23510415 pmcid: 3634360 doi: 10.1111/tan.12093

Gourraud, P. A. et al. HLA diversity in the 1000 genomes dataset. PLoS ONE 9, e97282 (2014).

pubmed: 24988075 pmcid: 4079705 doi: 10.1371/journal.pone.0097282

Smits, G. P., van Gageldonk, P. G., Schouls, L. M., van der Klis, F. R. & Berbers, G. A. Development of a bead-based multiplex immunoassay for simultaneous quantitative detection of IgG serum antibodies against measles, mumps, rubella, and varicella-zoster virus. Clin. Vaccine Immunol. 19, 396–400 (2012).

pubmed: 22237896 pmcid: 3294611 doi: 10.1128/CVI.05537-11

van Gageldonk, P. G., van Schaijk, F. G., van der Klis, F. R. & Berbers, G. A. Development and validation of a multiplex immunoassay for the simultaneous determination of serum antibodies to Bordetella pertussis, diphtheria and tetanus. J. Immunol. Methods 335, 79–89 (2008).

pubmed: 18407287 doi: 10.1016/j.jim.2008.02.018

de Voer, R. M., Schepp, R. M., Versteegh, F. G., van der Klis, F. R. & Berbers, G. A. Simultaneous detection of Haemophilus influenzae type b polysaccharide-specific antibodies and Neisseria meningitidis serogroup A, C, Y, and W-135 polysaccharide-specific antibodies in a fluorescent-bead-based multiplex immunoassay. Clin. Vaccin. Immunol. 16, 433–436 (2009).

doi: 10.1128/CVI.00364-08

Swart, E. M. et al. Long-term protection against diphtheria in the Netherlands after 50 years of vaccination: results from a seroepidemiological study. PLoS ONE 11, e0148605 (2016).

pubmed: 26863307 pmcid: 4749226 doi: 10.1371/journal.pone.0148605

Brinkman, I. D. et al. Early measles vaccination during an outbreak in the Netherlands: reduced short and long-term antibody responses in children vaccinated before 12 months of age. J. Infect. Dis. https://doi.org/10.1093/infdis/jiz159 (2019).

Bancroft, T. et al. Th1 versus Th2 T cell polarization by whole-cell and acellular childhood pertussis vaccines persists upon re-immunization in adolescence and adulthood. Cell Immunol. 304–305, 35–43 (2016).

pubmed: 27212461 pmcid: 4899275 doi: 10.1016/j.cellimm.2016.05.002

Lindestam Arlehamn, C. S. et al. Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3

pubmed: 23358848 pmcid: 3554618 doi: 10.1371/journal.ppat.1003130

Weiskopf, D. et al. Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8

pubmed: 23580623 pmcid: 3670335 doi: 10.1073/pnas.1305227110

Frazier, A. et al. Allergy-associated T cell epitope repertoires are surprisingly diverse and include non-IgE reactive antigens. World Allergy Organ. J. 7, 26 (2014).

pubmed: 25352946 pmcid: 4210551 doi: 10.1186/1939-4551-7-26

Schmiedel, B. J. et al. Impact of genetic polymorphisms on human immune cell gene expression resource impact of genetic polymorphisms on human immune cell gene expression. Cell 175, 1701–1715 (2018).

pubmed: 30449622 pmcid: 6289654 doi: 10.1016/j.cell.2018.10.022

Patterson, N., Price, A. L. & Reich, D. Population structure and eigenanalysis. PLoS Genet. 2, e190 (2006).

pubmed: 17194218 pmcid: 1713260 doi: 10.1371/journal.pgen.0020190

Gurdasani, D. et al. The African Genome Variation Project shapes medical genetics in Africa. Nature https://doi.org/10.1038/nature13997 (2015).

doi: 10.1038/nature13997 pubmed: 25470054

Delaneau, O., Marchini, J. & Zagury, J. F. A linear complexity phasing method for thousands of genomes. Nat. Methods 9, 179–181 (2011).

pubmed: 22138821 doi: 10.1038/nmeth.1785

Howie, B., Fuchsberger, C., Stephens, M., Marchini, J. & Abecasis, G. R. Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat. Genet. 44, 955–959 (2012).

pubmed: 22820512 pmcid: 3696580 doi: 10.1038/ng.2354

Keenan, K., McGinnity, P., Cross, T. F., Crozier, W. W. & Prodohl, P. A. DiveRsity: an R package for the estimation and exploration of population genetics parameters and their associated errors. Methods Ecol. Evol. 4, 782–788 (2013).

doi: 10.1111/2041-210X.12067

Henn, B. M. et al. Hunter-gatherer genomic diversity suggests a southern African origin for modern humans. Proc. Natl Acad. Sci. USA 108, 5154–5162 (2011).

pubmed: 21383195 pmcid: 3069156 doi: 10.1073/pnas.1017511108

Pirinen, M., Donnelly, P. & Spencer, C. C. Including known covariates can reduce power to detect genetic effects in case–control studies. Nat. Genet. 44, 848–851 (2012).

pubmed: 22820511 doi: 10.1038/ng.2346

Yang, J., Zaitlen, N. A., Goddard, M. E., Visscher, P. M. & Price, A. L. Advantages and pitfalls in the application of mixed-model association methods. Nat. Genet. https://doi.org/10.1038/ng.2876 (2014).

doi: 10.1038/ng.2876 pubmed: 25420146 pmcid: 4250049

Zhou, X. & Stephens, M. Efficient multivariate linear mixed model algorithms for genome-wide association studies. Nat. Methods 11, 407–409 (2014).

pubmed: 24531419 pmcid: 4211878 doi: 10.1038/nmeth.2848

Han, B. & Eskin, E. Random-effects model aimed at discovering associations in meta-analysis of genome-wide association studies. Am. J. Hum. Genet. 88, 586–598 (2011).

pubmed: 21565292 pmcid: 3146723 doi: 10.1016/j.ajhg.2011.04.014

Jia, X. et al. Imputing amino acid polymorphisms in human leukocyte antigens. PLoS ONE 8, e64683 (2013).

pubmed: 23762245 pmcid: 3675122 doi: 10.1371/journal.pone.0064683

Zheng, X. et al. HIBAG–HLA genotype imputation with attribute bagging. Pharmacogenomics J. 14, 192–200 (2014).

pubmed: 23712092 doi: 10.1038/tpj.2013.18

Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013).

pubmed: 23104886 doi: 10.1093/bioinformatics/bts635

Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014).

pubmed: 25516281 pmcid: 4302049 doi: 10.1186/s13059-014-0550-8

Shabalin, A. A. Matrix eQTL: ultra fast eQTL analysis via large matrix operations. Bioinformatics 28, 1353–1358 (2012).

pubmed: 22492648 pmcid: 3348564 doi: 10.1093/bioinformatics/bts163

Aguiar, V. R. C., César, J., Delaneau, O., Dermitzakis, E. T. & Meyer, D. Expression estimation and eQTL mapping for HLA genes with a personalized pipeline. PLoS Genet. 15, e1008091 (2019).

pubmed: 31009447 pmcid: 6497317 doi: 10.1371/journal.pgen.1008091

Vita, R. et al. The Immune Epitope Database (IEDB) 3.0. Nucleic Acids Res. 43, D405–D412 (2015).

pubmed: 25300482 doi: 10.1093/nar/gku938

Wang, P. et al. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics 11, 568 (2010).

pubmed: 21092157 pmcid: 2998531 doi: 10.1186/1471-2105-11-568

Mentzer, A. et al. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: summary statistics (1.0.0). Zenodo https://doi.org/10.5281/zenodo.7357687 (2022).

Mentzer, A. High-resolution African HLA resource uncovers HLA-DRB1 expression effects underlying vaccine response: script for testing amino-acid correlation (1.0.0).Zenodo https://doi.org/10.5281/zenodo.10728920 (2024).

doi: 10.5281/zenodo.10728920