? Overall Project Francisella tularensis is considered to be a Category A agent by the NIAID because of its extreme infectivity, ease of dissemination, and substantial capacity to cause illness and death. This Program Project brings together a diverse group of individuals with particular expertise in the fields of microbiology, cell biology, and mucosal immunology who are committed to continuing to explore in an integrated fashion, the pulmonary immune response to F. tularensis. Our group has made remarkable progress during the previous funding period as evidenced by, among other things, our multiple publications and the highly positive annual evaluations of our External Scientific Advisory Board. Of particular interest, we have recently demonstrated that mucosal vaccination with inactivated F. tularensis targeted to Fc receptors on antigen presenting cells or using an antioxidant mutant strain provides significant protection from pulmonary infection with the highly virulent SchuS4 strain. We now intend to build upon our achievements to: 1) Refine and further develop novel strategies for induction of anti-F. tularensis pulmonary immunity and determine the mechanisms responsible for protection. 2) Examine the coordinated intra- and extracellular recognition of F. tularensis. 3) Define the redox control of F. tularensis pathogenesis and its role in regulating immune protection. The overall goal of the Project continues to be development of vaccination platforms for effective protection at mucosal surfaces. A particular emphasis of the renewal application will be on complementary investigations that are focused on optimizing vaccine strategies to elicit protection against the highly virulent type A strain, SchuS4, in our fully approved animal BSL3.

Public Health Relevance

? Overall Project The overall goal of the Project continues to be development of vaccination platforms for effective protection at mucosal surfaces. The results of these studies will ultimately be used to evaluate novel mucosal vaccination strategies and new vaccine candidates against human respiratory infection with F. tularensis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
2P01AI056320-06A2
Application #
7690977
Study Section
Special Emphasis Panel (ZAI1-AR-M (M1))
Program Officer
Mukhopadhyay, Suman
Project Start
2003-09-30
Project End
2011-07-31
Budget Start
2009-08-14
Budget End
2010-07-31
Support Year
6
Fiscal Year
2009
Total Cost
$2,246,450
Indirect Cost
Name
Albany Medical College
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
190592162
City
Albany
State
NY
Country
United States
Zip Code
12208
Sunagar, Raju; Kumar, Sudeep; Rosa, Sarah J et al. (2018) Differential In Vitro Cultivation of Francisella tularensis Influences Live Vaccine Protective Efficacy by Altering the Immune Response. Front Immunol 9:1594
Nagar, Abhinit; DeMarco, Richard A; Harton, Jonathan A (2018) Inflammasome and Caspase-1 Activity Characterization and Evaluation: An Imaging Flow Cytometer-Based Detection and Assessment of Inflammasome Specks and Caspase-1 Activation. J Immunol :
Drake, James R (2018) The immunobiology of ubiquitin-dependent B cell receptor functions. Mol Immunol 101:146-154
Alqahtani, Maha; Ma, Zhuo; Ketkar, Harshada et al. (2018) Characterization of a Unique Outer Membrane Protein Required for Oxidative Stress Resistance and Virulence of Francisella tularensis. J Bacteriol 200:
Steiner, Donald J; Furuya, Yoichi; Metzger, Dennis W (2018) Detrimental Influence of Alveolar Macrophages on Protective Humoral Immunity during Francisella tularensis SchuS4 Pulmonary Infection. Infect Immun 86:
Chen, Fei; Cui, Guolin; Wang, Shuxia et al. (2017) Outer membrane vesicle-associated lipase FtlA enhances cellular invasion and virulence in Francisella tularensis LVS. Emerg Microbes Infect 6:e66
Periasamy, Sivakumar; Porter, Kristen A; Atianand, Maninjay K et al. (2017) Pyrin-only protein 2 limits inflammation but improves protection against bacteria. Nat Commun 8:15564
Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean et al. (2017) Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice. Vaccine 35:4997-5005
Holland, Kristen M; Rosa, Sarah J; Kristjansdottir, Kolbrun et al. (2017) Differential Growth of Francisella tularensis, Which Alters Expression of Virulence Factors, Dominant Antigens, and Surface-Carbohydrate Synthases, Governs the Apparent Virulence of Ft SchuS4 to Immunized Animals. Front Microbiol 8:1158
Duffy, Ellen B; Periasamy, Sivakumar; Hunt, Danielle et al. (2016) Fc?R mediates TLR2- and Syk-dependent NLRP3 inflammasome activation by inactivated Francisella tularensis LVS immune complexes. J Leukoc Biol 100:1335-1347

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