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


CONCLUSIONS
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.


CONCLUSIONS
Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.
Dhiman
Neelam
N
Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minn, USA.
Poland
Gregory A
GA
Cunningham
Julie M
JM
Jacobson
Robert M
RM
Ovsyannikova
Inna G
IG
Vierkant
Robert A
RA
Wu
Yanhong
Y
Pankratz
V Shane
VS
D000293:Adolescent; D000917:Antibody Formation / Q000235:genetics*; D015703:Antigens, CD / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008458:Measles Vaccine / Q000276:immunology*; D008459:Measles virus / Q000276:immunology; D051916:Membrane Cofactor Protein / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D007074:Immunoglobulin G; D008458:Measles Vaccine; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1