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.
Poland, G A; Ovsyannikova, I G; Kennedy, R B (2018) Personalized vaccinology: A review. Vaccine 36:5350-5357 |
Haralambieva, Iana H; Ovsyannikova, Inna G; Kennedy, Richard B et al. (2018) Detection and Quantification of Influenza A/H1N1 Virus-Specific Memory B Cells in Human PBMCs Using ELISpot Assay. Methods Mol Biol 1808:221-236 |
Poland, Gregory A (2018) Influenza vaccine failure: failure to protect or failure to understand? Expert Rev Vaccines 17:495-502 |
Voigt, Emily A; Grill, Diane E; Zimmermann, Michael T et al. (2018) Transcriptomic signatures of cellular and humoral immune responses in older adults after seasonal influenza vaccination identified by data-driven clustering. Sci Rep 8:739 |
Sweeney, Timothy E; Wynn, James L; Cernada, MarĂa et al. (2018) Validation of the Sepsis MetaScore for Diagnosis of Neonatal Sepsis. J Pediatric Infect Dis Soc 7:129-135 |
Sweeney, Timothy E; Khatri, Purvesh (2017) Benchmarking Sepsis Gene Expression Diagnostics Using Public Data. Crit Care Med 45:1-10 |
Haynes, Winston A; Vallania, Francesco; Liu, Charles et al. (2017) EMPOWERING MULTI-COHORT GENE EXPRESSION ANALYSIS TO INCREASE REPRODUCIBILITY. Pac Symp Biocomput 22:144-153 |
Mpina, Maxmillian; Maurice, Nicholas J; Yajima, Masanao et al. (2017) Controlled Human Malaria Infection Leads to Long-Lasting Changes in Innate and Innate-like Lymphocyte Populations. J Immunol 199:107-118 |
Sweeney, Timothy E; Khatri, Purvesh (2017) The authors reply. Crit Care Med 45:e457-e458 |
Jiang, Dadi; Turner, Brandon; Song, Jie et al. (2017) Comprehensive Analysis of the Unfolded Protein Response in Breast Cancer Subtypes. JCO Precis Oncol 2017: |
Showing the most recent 10 out of 55 publications