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VACCINOMICS: CURRENT FINDINGS, CHALLENGES AND NOVEL APPROACHES FOR VACCINE DEVELOPMENT Megan Brown Dr. Inna G. Ovsyannikova and Dr. Gregory A. Poland
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Key Terms Vaccinomics To identify and understand genetic markers of immune response in order to provide new vaccine approaches Immunogenetics Studies the relationship between the immune system and genetics HLA genes Part of the human leukocyte antigen (HLA) system The major histocompatibility complex (MHC) in humans Primary genes responsible for immune function
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Why study this? To ensure that our vaccine technology evolves to best combat emerging pathogens To improve immune response from patients To see the effects of various genes on immune responses in differing individuals Using population-based gene studies/SNP association studies To understand the ties between vaccine-specific immunity and immune response gene variants To encourage the use of new sequencing technologies and bioinformatics towards to further study the relationship between genetics and immune response
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Things to note Vaccine response is largely heritable Twin studies Focus on HLA class I and II genes Deliver pathogen-derived peptide epitopes (antigenic determinants) to Tcells Significant polymorphisms
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Rubella genotyping study 738 children Examined candidate SNPs and haplotypes, and their relationship to immune measures Found that cytokine and cytokine receptor genetic variants were responsible for both cytokine and humoral responses The point: developing a vaccine that included cytokines to “fill in the gaps” could provide improved immunity
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Innate Genes The immune system is complex; as such, genes outside of the MHC are important Toll-like receptors (TLR) Pattern recognition receptors Detect viruses by sensing RNA and viral proteins The point: new vaccines using adjuvants that target non-HLA genes have been very effective
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The future of this field Genome-wide studies SNP association with markers of immunity to pathogens Next Generation Sequencing (NGS) Identify rare polymorphisms, alternative splice variants, copy number variants, and their relationship to immune response Improve knowledge of immune response mechanisms in combination with immunogenetic data
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