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

• Published in: Journal of allergy and clinical immunology Vol. 120; no. 3; pp. 666 - 672
• Main Authors: Dhiman, Neelam, Poland, Gregory A., Cunningham, Julie M., Jacobson, Robert M., Ovsyannikova, Inna G., Vierkant, Robert A., Wu, Yanhong, Pankratz, V. Shane
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.09.2007; Elsevier; Elsevier Limited
• Subjects: Adolescent; Allergy and Immunology; Antibody Formation - genetics; Antigens, CD - genetics; Biological and medical sciences; CD46; Child; Children & youth; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes; Humans; Immunoglobulin G - blood; Immunopathology; Male; Measles vaccine; Measles Vaccine - immunology; Measles virus - immunology; measles virus receptors; Medical sciences; Membrane Cofactor Protein - genetics; Mumps; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptors, Cell Surface - genetics; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Signaling Lymphocytic Activation Molecule Family Member 1; signaling lymphocyte activation molecule; single nucleotide polymorphisms; Vaccines; measles virus receptors; MMR; SCR; SLAM; Measles vaccine; signaling lymphocyte activation molecule; SNP; LD; single nucleotide polymorphisms; CD46; ΔA; Linkage disequilibrium; Short consensus repeat; Change in absorbance; Signaling lymphocyte activation molecule; Single nucleotide polymorphism; Measles-mumps-rubella; Immunopathology; Genetic variability; Acquired immunity; Genotype; Vaccine; Paramyxoviridae; Infection; Virus; Prevention; Paramyxovirinae; Mononegavirales; Immunology; Viral disease; Measles; Morbillivirus; Humoral immunity; Biological receptor; Measles virus
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2007.04.036

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. We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. 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. 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. 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. Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.