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.
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.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom. catrin@tropmedres.ac
Catrin E
CE
Moore
Branwen J
BJ
Hennig
Kirsten P
KP
Perrett
J Claire
JC
Hoe
Sue J
SJ
Lee
Helen
H
Fletcher
Denise
D
Brocklebank
Daniel
D
O'Connor
Matthew D
MD
Snape
Andrew J
AJ
Hall
Shelley
S
Segal
Adrian V S
AV
Hill
Andrew J
AJ
Pollard
D000293:Adolescent; D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D013997:Time Factors; D051196:Toll-Like Receptor 3 / Q000235:genetics*; D055815:Young Adult
D000907:Antibodies, Bacterial; C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3; C410218:serogroup C meningococcal conjugate vaccine