The Association of CD46, SLAM and CD209 Cellular Receptor Gene SNPs with Variations in Measles Vaccine-Induced Immune Responses: A Replication Study and Examination of Novel Polymorphisms

Tuesday, 21st of January 2014

[source]Human Heredity[|source]

While Measles Virus (MV) vaccine induces both humoral and CMI responses, the duration of protective immunity is shorter than that of acquired immunity during infection with wild-type virus. MV interacts with two known cellular receptors – CD46 (a complement regulatory protein) and SLAM (signaling lymphocyte activation molecule, CDw150). CD46 and SLAM act as cellular receptors for laboratory-adapted and vaccine strains, while wild-type MV strains preferentially utilize SLAM as a receptor.

In this report, the authors examined associations between serum neutralizing proteins in the CD46, SLAM and CD209 genes and measures of measles vaccine-specific cellular (secreted cytokines and IFN-γ Elispot cytokine-producing cells) immunity in a cohort of 764 healthy subjects after receipt of two doses of measles vaccine. Findings and additional details are available at:  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3242703/

 

Abstract

Background: The measles virus (MV) interacts with two known cellular receptors: CD46 and SLAM. The transmembrane receptor CD209 interacts with MV and augments dendritic cell infection.

Methods: 764 subjects previously immunized with measles-mumps-rubella vaccine were genotyped for 66 candidate SNPs in the CD46, SLAM and CD209 genes as part of a larger study.

Results: A previously detected association of the CD46 SNP rs2724384 with measles-specific antibodies was successfully replicated in this study. Increased representation of the minor allele G for an intronic CD46 SNP was associated with an allele dose-related decrease (978 vs. 522 mIU/ml, p = 0.0007) in antibody levels. This polymorphism rs2724384 also demonstrated associations with IL-6 (p = 0.02), IFN-α (p = 0.007) and TNF-α (p = 0.0007) responses. Two polymorphisms (coding rs164288 and intronic rs11265452) in the SLAM gene that were associated with measles antibody levels in our previous study were associated with IFN-γ Elispot (p = 0.04) and IL-10 responses (p = 0.0008), respectively, in this study. We found associations between haplotypes, AACGGAATGGAAAG (p = 0.009) and GGCCGAGAGGAGAG (p < 0.001), in the CD46 gene and TNF-α secretion.

Conclusion: Understanding the functional and mechanistic consequences of these genetic polymorphisms on immune response variations could assist in directing new measles and potentially other viral vaccine design, and in better understanding measles immunogenetics