Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors

J Allergy Clin Immunol. 2007 Sep;120(3):666-72. doi: 10.1016/j.jaci.2007.04.036. Epub 2007 Jun 8.

Abstract

Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine.

Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response.

Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs.

Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies.

Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination.

Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibody Formation / genetics*
  • Antigens, CD / genetics*
  • Child
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Male
  • Measles Vaccine / immunology*
  • Measles virus / immunology
  • Membrane Cofactor Protein / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / genetics*
  • Signaling Lymphocytic Activation Molecule Family Member 1

Substances

  • Antigens, CD
  • Immunoglobulin G
  • Measles Vaccine
  • Membrane Cofactor Protein
  • Receptors, Cell Surface
  • Signaling Lymphocytic Activation Molecule Family Member 1