This Cooperative Center for Translational Research on Human Immunology and Biodefense is entitled 'Influenza Immunity: Protective Mechanisms against a Pandemic Respiratory Virus'. Our objective is to use vaccine-induced and naturally acquired influenza A immunity as a model for comprehensive, integrated analyses of adaptive and innate immune mechanisms and antimicrobial protection of the respiratory tract in children and adults. Influenza immunology is relevant to biodefense because influenza A has significant potential to be modified genetically to create a bioterrorist agent. Further, influenza A causes natural pandemics, which can incapacitate a large fraction of the population, endangering preparedness. Influenza A has many characteristics of microbial pathogens that could become agents of civilian bioterrorism. Among these are: capacity to cause illness with high morbidity and mortality, highly efficient person-to-person transmission, high infectivity by aerosol, resulting in the capacity to cause large outbreaks, potential to cause anxiety in the public, and potential to be weaponized. While influenza vaccines exist, the immunologic mechanisms by which protection is induced in the respiratory tact are poorly understood in the human host. Genetically altered influenza A viruses that express unique hemagglutinin (HA) and neuraminidase (NA) proteins have the capacity to infect all age groups. In a biodefense context, the rapidity with which protection can be elicited in a non-immune population is critical. The influenza A model is expected to allow a better definition of specialized adaptive B cell and T cell immune mechanisms that control infections of the respiratory system. Our investigative approach also encompasses the study of innate, natural killer cell responses to influenza, in parallel with acquisition of adaptive immunity in children and adults. Comparing influenza vaccines will identify differences when the host responds to parenterally administered, inactivated antigens, versus live attenuated virus delivered via the respiratory route. At our Center, investigators leading the Research Resource Technical Development component and the Research Projects will undertake rapid translation of basic immunology methods into applications for analyzing innate and acquired influenza A immunity. These innovations will have broad relevance for understanding human immunity against microbial pathogens of concern for biodefense.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
3U19AI057229-06S1
Application #
7846526
Study Section
Special Emphasis Panel (ZAI1-KS-I (J4))
Program Officer
Quill, Helen R
Project Start
2009-06-05
Project End
2010-09-30
Budget Start
2009-06-05
Budget End
2010-09-30
Support Year
6
Fiscal Year
2009
Total Cost
$79,610
Indirect Cost
Name
Stanford University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Sweeney, Timothy E; Azad, Tej D; Donato, Michele et al. (2018) Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters. Crit Care Med 46:915-925
Lin, Dongxia; Maecker, Holden T (2018) Mass Cytometry Assays for Antigen-Specific T Cells Using CyTOF. Methods Mol Biol 1678:37-47
Goltsev, Yury; Samusik, Nikolay; Kennedy-Darling, Julia et al. (2018) Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging. Cell 174:968-981.e15
Gee, Marvin H; Sibener, Leah V; Birnbaum, Michael E et al. (2018) Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro. Proc Natl Acad Sci U S A 115:E7369-E7378
Cheung, Peggie; Vallania, Francesco; Warsinske, Hayley C et al. (2018) Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with Aging. Cell 173:1385-1397.e14
Mamedov, Murad R; Scholzen, Anja; Nair, Ramesh V et al. (2018) A Macrophage Colony-Stimulating-Factor-Producing ?? T Cell Subset Prevents Malarial Parasitemic Recurrence. Immunity 48:350-363.e7
Kooreman, Nigel G; Kim, Youngkyun; de Almeida, Patricia E et al. (2018) Autologous iPSC-Based Vaccines Elicit Anti-tumor Responses In Vivo. Cell Stem Cell 22:501-513.e7
Haynes, Winston A; Tomczak, Aurelie; Khatri, Purvesh (2018) Gene annotation bias impedes biomedical research. Sci Rep 8:1362
Sweeney, Timothy E; Thomas, Neal J; Howrylak, Judie A et al. (2018) Multicohort Analysis of Whole-Blood Gene Expression Data Does Not Form a Robust Diagnostic for Acute Respiratory Distress Syndrome. Crit Care Med 46:244-251
Kronstad, Lisa M; Seiler, Christof; Vergara, Rosemary et al. (2018) Differential Induction of IFN-? and Modulation of CD112 and CD54 Expression Govern the Magnitude of NK Cell IFN-? Response to Influenza A Viruses. J Immunol 201:2117-2131

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