Francisella tularensis (F. tularensis) has many characteristics that warrant its classification as a category A pathogen and potential bioweapon. It is easy to grow and as an aerosol, it has a high rate of infection in exposed populations. The tularemia vaccine history is remarkable in that the Live Vaccine Strain (LVS) demonstrated protection in nonhuman primates and humans but FDA approval was problematic because the basis and stability of its attenuation has not been identified. Identification of vaccine candidates encoded by the F. tularensis genome that induce protection could lead to a subunit vaccine. We have developed a murine model for primary pulmonary infection with Biovar A virulent F. tularensis for which LVS induces a protective response against a respiratory challenge with virulent F. tularensis. We intend to study the lung-pathogen interaction during the acquired responses for F. tularensis in mice and primates. We have partnered with MacroGenics, a vaccine candidate discovery company, and Lovelace Respiratory Research Institute (LRRI). Using expression library immunization, we will identify protective epitopes encoded by the virulent F. tularensis genome that will lead to a vaccine. Finally, the vaccine candidates will be tested in a nonhuman primate model of aerosolized F. tularensis.
Aim 1. Determine the role for specific immune cells and inflammatory mediators in the lung during the acquired pulmonary immune response to Biovar A F. tularensis.
Aim 2. Identify new subunit vaccine candidates against F. tularensis using expression library immunization Aim 3. Determine the clinical phenotype and characterize the host response to pneumonic tularemia in the non-human primate model, providing critical background data to permit efficient testing of vaccine candidates in the model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI056295-04
Application #
7632082
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
4
Fiscal Year
2008
Total Cost
$200,491
Indirect Cost
Name
University of New Mexico
Department
Type
DUNS #
868853094
City
Albuquerque
State
NM
Country
United States
Zip Code
87131
Hutt, Julie A; Lovchik, Julie A; Drysdale, Melissa et al. (2014) Lethal factor, but not edema factor, is required to cause fatal anthrax in cynomolgus macaques after pulmonary spore challenge. Am J Pathol 184:3205-16
Lovchik, Julie A; Drysdale, Melissa; Koehler, Theresa M et al. (2012) Expression of either lethal toxin or edema toxin by Bacillus anthracis is sufficient for virulence in a rabbit model of inhalational anthrax. Infect Immun 80:2414-25
Mara-Koosham, Gopi; Hutt, Julie A; Lyons, C Rick et al. (2011) Antibodies contribute to effective vaccination against respiratory infection by type A Francisella tularensis strains. Infect Immun 79:1770-8
Hansen, Spencer J; Rushton, John; Dekonenko, Alexander et al. (2011) Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection. Virology 412:411-25
Chand, Hitendra S; Schuyler, Mark; Joste, Nancy et al. (2010) Anti-IgE therapy results in decreased myeloid dendritic cells in asthmatic airways. J Allergy Clin Immunol 125:1157-1158.e5
Lipscomb, Mary F; Hutt, Julie; Lovchik, Julie et al. (2010) The pathogenesis of acute pulmonary viral and bacterial infections: investigations in animal models. Annu Rev Pathol 5:223-52
Borovkov, Alex Y; Loskutov, Andrey V; Robida, Mark D et al. (2010) High-quality gene assembly directly from unpurified mixtures of microarray-synthesized oligonucleotides. Nucleic Acids Res 38:e180
Wu, Terry H; Zsemlye, Jason L; Statom, Gloria L et al. (2009) Vaccination of Fischer 344 rats against pulmonary infections by Francisella tularensis type A strains. Vaccine 27:4684-93
Collazo, Carmen M; Meierovics, Anda I; De Pascalis, Roberto et al. (2009) T cells from lungs and livers of Francisella tularensis-immune mice control the growth of intracellular bacteria. Infect Immun 77:2010-21
Hahn, Andrew C; Lyons, C Rick; Lipscomb, Mary F (2008) Effect of Bacillus anthracis virulence factors on human dendritic cell activation. Hum Immunol 69:552-61

Showing the most recent 10 out of 12 publications