1. VACCINOMICS: CURRENT FINDINGS, CHALLENGES AND NOVEL APPROACHES FOR VACCINE DEVELOPMENT Megan Brown Dr. Inna G. Ovsyannikova and Dr. Gregory A. Poland

2. 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

3. 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

5. 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

7. 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

8. 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

9. 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