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Title: Host genetic variation is a contributable factor for imperfectly-immunizing vaccination

item Zhang, Huanmin

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/2/2012
Publication Date: 8/15/2012
Citation: Zhang, H. 2012. Host genetic variation is a contributable factor for imperfectly-immunizing vaccination. Meeting Abstract. RAPIDD Imprefectly Immunizing Vaccine Workshop, August 15-17, 2012, Dearborn, MI.

Interpretive Summary:

Technical Abstract: Vaccine protective efficacy is determined by multiple factors including host genetics, vaccine type, vaccine dosage, challenge virus virulence, challenge virus dose, and interval between vaccination and exposure to challenge viruses. About two decades ago, studies conducted to evaluate host genetic effect on vaccine protective efficacy using chickens from a series of B-congenic strains concluded that major histocompatibility complex (MHC) B haplotype significantly affect vaccine protective efficacy. Recent studies using chickens from highly inbred and specific pathogen free lines sharing a common MHC (B*2) haplotype provide experimental evidence that non-MHC genetic background of chickens also plays an important role in modulating vaccine protective efficacy. Striking difference in protection against a very virulent Marek’s disease (MD) virus challenge was observed between MD resistant and susceptible lines of chickens, which shared a same B haplotype. Genome-Wide SNP scan identified 14,925 SNPs mainly residing on chromosomes 1-15, 17-28 and Z, out of 57,636 SNPs, that differ between two of the lines. DNA methylation level, an epigenetic factor, was found to differ between the lines at promoter regions of genes with hypomethylation, intermediate methylation, or hypermethylation levels. Differential gene and miRNA expressions were also observed between the lines of chickens. Taken all together, our data suggest host genetic variation is probably a major contributor in determination of how well a vaccine protects against pathogenicity upon viral infection. A better understanding of the roles of host genetics in response to vaccines will serve as the touchstone for rational design and development of novel safe and effective vaccines.