MEASLES VIRUS RECEPTOR POLYMORPHISMS INFLUENCE RECEPTOR PROTEIN EXPRESSION AND PRIMARY MEASLES VACCINE RESPONSES IN NAIVE AUSTRALIAN CHILDREN

Monday, 14th of April 2014

[source]Clinical and Vaccine Immunology[|source]

Host immunogenetics is likely to be a critical factor in the modulation of vaccine responses, with measles vaccine antibody responses in particular shown to have high heritability. In previously primed school children and adults, associations have been identified with human leukocyte antigen (HLA) alleles, cytokine and cytokine receptor genes, MV receptor genes, and Toll-like receptors. However, the influence of genetic variants on measles vaccine responses in naive infants immediately following their first vaccination has not been previously elucidated.

 

In this report, the authors investigated associations between CD46 polymorphisms and measles IgG levels in a population of naive infants from Perth, Australia after their first measles vaccination. In addition, the authors also report on their investigation of the associations of the CD46 polymorphisms with functional effects on receptor protein expression to perhaps suggest a mechanistic link between genetic variants and measles antibody responses.  Findings, discussions, conclusions and recommendations are accessible at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346334/

 

ABSTRACT

Despite the availability of measles vaccines, infants continue to die from measles. Measles vaccine responses vary between individuals, and poor immunogenicity is likely to preclude protection against measles. CD46 is a ubiquitously expressed specific receptor for vaccine strains of measles virus. CD46polymorphisms have not been functionally investigated but may affect CD46 protein expression, which in turn may mediate primary measles antibody responses in infants. In a cohort of children aged 12 to 14 months from Perth, Australia (n = 137), after their first dose of measles-mumps-rubella (MMR) vaccine, CD46 polymorphisms were genotyped, and post vaccination measles IgG and CD46 protein expression before and after measles lysate stimulation of cells were measured. Three CD46 variants (rs7144, rs11118580, and rs2724384) were significantly associated with measles virus-specific IgG levels (P = 0.008, P = 0.026, and P = 0.018, respectively). There were significant differences between CD46rs7144 genotypes and CD46 protein expression on T cells, as well as the down regulation of CD46 and T-cell frequency after measles lysate stimulation. We show that CD46 polymorphisms were associated with primary measles antibody responses in naive infants. We also report the first association of a measles virus receptor polymorphism with functional effects on the receptor, suggesting a possible mechanism through which antibody responses are altered. Elucidating all of the interconnecting genetic factors that alter primary measles vaccine responses may be important for identifying children at risk of poor immunogenicity or vaccine failure and for the future design of vaccine strategies to help these children.