This application is for funding of a study to characterize the human immune response before and after 2010-2011 influenza A/California/H1N1 seasonal vaccination by developing comprehensive immune profiles utilizing systems biology and bioinformatics approaches. We will develop novel comprehensive immune profiles using a systems biology approach to define specific immune profiles that discriminate baseline, early, mid, and late (homeostatic) innate, humoral, and cellular immune responses after immunization among older adults. Our broad objective is to create comprehensive and innovative immune profiles that explain and predict variations in immune responses to influenza A/H1N1 vaccines. Using novel bioinformatic approaches and a comprehensive assay set (immune outcomes, immune profiles, and immunosenescence markers), we v /ill create models of immune profiling that are the focus of this application, among pre- and postimmunosenescent subjects. To accomplish these goals, we propose the following specific aims: 1) To describe and characterize longitudinal immune system profiles (Day 0 to Day 75) before and after influenza A/H1N1 vaccination, 2) To identify immune profiles that correlate with vaccine immunogenicity at the humoral and cellular levels Day 0 to Day 75 after vaccination, and 3) To replicate and verify the immune profiles and models discovered in Specific Aims 1-2 in a new replication cohort. This proposal is innovative and significant in that it will: Utilize cutting edge technology that has not previously been applied to understanding influenza A vaccine-induced immune responses. Create comprehensive immune profiles that provide a model and a framework that describe and explain the variability of immune responses to influenza A vaccine in the continuum from baseline, early, mid (peak), and late (homeostatic) immune responses after antigenic challenge. Provide general knowledge important to the development of new influenza vaccines. The end result of this series of aims will be the first systematic immune profiles and models of influenza A vaccine-specific immunogenicity using novel high dimensional technology and bioinformatics approaches, and has the potential to set the standard for analytical methods to understand complex biologic systems. Relevance to Public Health: This grant will provide novel information describing how immune responses to inactivated influenza A/H1N1 vaccine are generated. This information is useful in designing new vaccines to control this deadly viral disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZAI1)
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Deckhut Augustine, Alison M
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Mayo Clinic, Rochester
United States
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Zimmermann, Michael T; Oberg, Ann L; Grill, Diane E et al. (2016) System-Wide Associations between DNA-Methylation, Gene Expression, and Humoral Immune Response to Influenza Vaccination. PLoS One 11:e0152034
Poland, Gregory A; Whitaker, Jennifer A; Poland, Caroline M et al. (2016) Vaccinology in the third millennium: scientific and social challenges. Curr Opin Virol 17:116-25
Sweeney, Timothy E; Braviak, Lindsay; Tato, Cristina M et al. (2016) Genome-wide expression for diagnosis of pulmonary tuberculosis: a multicohort analysis. Lancet Respir Med 4:213-24
Kennedy, Richard B; Ovsyannikova, Inna G; Haralambieva, Iana H et al. (2016) Immunosenescence-Related Transcriptomic and Immunologic Changes in Older Individuals Following Influenza Vaccination. Front Immunol 7:450
Fang, Fengqin; Yu, Mingcan; Cavanagh, Mary M et al. (2016) Expression of CD39 on Activated T Cells Impairs their Survival in Older Individuals. Cell Rep 14:1218-31
Hsiao, Chiaowen; Liu, Mengya; Stanton, Rick et al. (2016) Mapping cell populations in flow cytometry data for cross-sample comparison using the Friedman-Rafsky test statistic as a distance measure. Cytometry A 89:71-88
Kennedy, Richard B; Simon, Whitney L; Gibson, Michael J et al. (2016) The composition of immune cells serves as a predictor of adaptive immunity in a cohort of 50- to 74-year-old adults. Immunology 148:266-75
Haynes, Winston A; Vallania, Francesco; Liu, Charles et al. (2016) EMPOWERING MULTI-COHORT GENE EXPRESSION ANALYSIS TO INCREASE REPRODUCIBILITY. Pac Symp Biocomput 22:144-153
Rahmani, Bahareh; Zimmermann, Michael T; Grill, Diane E et al. (2016) Recursive Indirect-Paths Modularity (RIP-M) for Detecting Community Structure in RNA-Seq Co-expression Networks. Front Genet 7:80
Ovsyannikova, I G; Salk, H M; Kennedy, R B et al. (2016) Gene signatures associated with adaptive humoral immunity following seasonal influenza A/H1N1 vaccination. Genes Immun 17:371-379

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