Abstract

Program Director/Principal Investigator (Last, First, Middle): Hook, MagnUS PROJECT SUMMARY (Seeinstructions): We have made the remarkable discovery that a crude bacterial lysate can stimulate the lung innate immune system, resulting in broad protection against pathogenic microorganisms including agents of bioterror. Moreover, we have identified a single bacterial protein, Ef2505, that has the ability to induce Stimulated Innate Resistance (StIR) to an extent similar to that observed with the crude bacterial lysate. These discoveries represent the bases for the current proposal, the ultimate goal of which is to develop and test a clinically active immunostimulant that can be used to protect against a broad range of microbial bioterror agents. To accomplish this, we have assembled a research team with complimentary expertise in order to determine the molecular mechanisms that cause StIR, which we believe will be required for FDA approval of the product. In addition, we will develop a prototype product and demonstrate its ability to protect against in vivo infections with Bacillis anthracis, Yersinia pestis and Francisella tularensis in mouse models.

Public Health Relevance

PROJECT/

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project--Cooperative Agreements (U01)
Project #
7U01AI082226-04
Application #
8309290
Study Section
Special Emphasis Panel (ZAI1-BLG-M (J1))
Program Officer
Zou, Lanling
Project Start
2009-07-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$450,594
Indirect Cost
$56,279

  Institution

Name
Texas A&M University
Department
Type
Schools of Medicine
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845

  Publications

Cleaver, J O; You, D; Michaud, D R et al. (2014) Lung epithelial cells are essential effectors of inducible resistance to pneumonia. Mucosal Immunol 7:78-88
Tuvim, Michael J; Gilbert, Brian E; Dickey, Burton F et al. (2012) Synergistic TLR2/6 and TLR9 activation protects mice against lethal influenza pneumonia. PLoS One 7:e30596
Evans, Scott E; Tuvim, Michael J; Fox, Cory J et al. (2011) Inhaled innate immune ligands to prevent pneumonia. Br J Pharmacol 163:195-206
Duggan, Jeffrey M; You, Dahui; Cleaver, Jeffrey O et al. (2011) Synergistic interactions of TLR2/6 and TLR9 induce a high level of resistance to lung infection in mice. J Immunol 186:5916-26
Evans, Scott E; Xu, Yi; Tuvim, Michael J et al. (2010) Inducible innate resistance of lung epithelium to infection. Annu Rev Physiol 72:413-35
Evans, Scott E; Scott, Brenton L; Clement, Cecilia G et al. (2010) Stimulated innate resistance of lung epithelium protects mice broadly against bacteria and fungi. Am J Respir Cell Mol Biol 42:40-50