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Cell Rep. 2019 Jun 11;27(11):3241-3253.e4. doi: 10.1016/j.celrep.2019.05.053.

Common Genetic Variations Associated with the Persistence of Immunity following Childhood Immunization.

Author information

1
Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK. Electronic address: daniel.oconnor@paediatrics.ox.ac.uk.
2
Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
3
Department of Paediatrics, University of Oxford, Oxford, UK; NIHR Oxford Biomedical Research Centre, Oxford, UK.
4
NIHR Oxford Biomedical Research Centre, Oxford, UK; Wellcome Centre for Human Genetics, University of Oxford, Oxford, UK.
5
Centre for Infectious Disease Control Netherlands, RIVM, Bilthoven, the Netherlands.
6
Division of Infectious Diseases, Department of Medicine, Imperial College London, London, UK.
7
Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Department of Pathogen Molecular Biology, London School of Hygiene & Tropical Medicine, London, UK.

Abstract

Vaccines have revolutionized public health, preventing millions of deaths each year, particularly in childhood. Yet, there is considerable variability in the magnitude and persistence of vaccine-induced immunity. Maintenance of specific antibody is essential for continuity of vaccine-induced serological protection. We conducted a genome-wide association study into the persistence of immunity to three childhood vaccines: capsular group C meningococcal (MenC), Haemophilus influenzae type b, and tetanus toxoid (TT) vaccines. We detail associations between variants in a locus containing a family of signal-regulatory proteins and the persistence MenC immunity. We postulate a regulatory role for the lead SNP, with supporting epigenetic and expression quantitative trait loci data. Furthermore, we define associations between SNPs in the human leukocyte antigen (HLA) locus and the persistence of TT-specific immunity. Moreover, we describe four classical HLA alleles, HLA DRB10301, HLA DQB10201, HLA DQB10602, and HLA DRB11501, associated with TT-specific immunity, independent of the lead SNP association.

KEYWORDS:

GWAS; HLA; SIRPG; meningococcal disease; persistence of immunity; vaccine-induced immunity

PMID:
31189108
DOI:
10.1016/j.celrep.2019.05.053
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