Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine

Moore, CE; Hennig, BJ; Perrett, KP; Hoe, JC; Lee, SJ; Fletcher, H; Brocklebank, D; O'Connor, D; Snape, MD; Hall, AJ; Segal, S; Hill, AVS; Pollard, AJ; (2012) Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine. Clinical and vaccine immunology , 19 (3). pp. 295-303. ISSN 1556-6811 DOI: 10.1128/CVI.05379-11

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Abstract

The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P = 0.004 [unadjusted]) and CD44 (rs12419062) (P = 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.

Item Type: Article
Keywords: linked-immunosorbent-assay, united-kingdom, haemophilus-influenzae, human-antibody, polysaccharide, responses, susceptibility, infection, protection, children, Adolescent, Antibodies, Bacterial, blood, Antigens, CD44, genetics, Blood Bactericidal Activity, Child, Child, Preschool, Female, Genetic Association Studies, Humans, Immunoglobulin G, blood, Infant, Male, Meningococcal Infections, immunology, prevention & control, Meningococcal Vaccines, immunology, Polymorphism, Single Nucleotide, Time Factors, Toll-Like Receptor 3, genetics, Young Adult
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- ) > Dept of Nutrition and Public Health Interventions Research (2003-2012)
Faculty of Epidemiology and Population Health > Dept of Population Health (2012- )
Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 22205660
Web of Science ID: 300841200001
URI: http://researchonline.lshtm.ac.uk/id/eprint/24950

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