Significant progress has been made over the past few years in identifying new vaccine candidates that could potentially be used for the prevention or immunotherapy of tuberculosis in human beings. The purpose of this proposed project is to take a select few of these vaccine candidates and perform longer term efficacy and safety evaluations to see which are the most robust. The animal model to be used will be the low dose aerosol challenge in the guinea pig, an animal which provides a stringent test given its susceptibility to infection and similarities in immunopathology to human disease. The central hypothesis to be tested will be that different vaccines, given data that their immunologic targets may differ, may behave differently in their ability to modulate, delay, or prevent the development of the disease process. To facilitate this analysis, we will use as a template our recent definition of four discrete phases of the granulomatous process in the lungs of infected guinea pigs, The proposed studies are lengthy, and unavoidably expensive, but should provide a basic framework upon which a standardized procedure for efficacy and safety testing of new tuberculosis vaccines can be based. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI054697-04
Application #
7029594
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Lacourciere, Karen A
Project Start
2003-03-01
Project End
2008-02-29
Budget Start
2006-03-01
Budget End
2007-02-28
Support Year
4
Fiscal Year
2006
Total Cost
$642,082
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Basaraba, Randall J; Bielefeldt-Ohmann, Helle; Eschelbach, Ellie K et al. (2008) Increased expression of host iron-binding proteins precedes iron accumulation and calcification of primary lung lesions in experimental tuberculosis in the guinea pig. Tuberculosis (Edinb) 88:69-79
Palanisamy, Gopinath S; Smith, Erin E; Shanley, Crystal A et al. (2008) Disseminated disease severity as a measure of virulence of Mycobacterium tuberculosis in the guinea pig model. Tuberculosis (Edinb) 88:295-306
Ordway, Diane; Henao-Tamayo, Marcela; Shanley, Crystal et al. (2008) Influence of Mycobacterium bovis BCG vaccination on cellular immune response of guinea pigs challenged with Mycobacterium tuberculosis. Clin Vaccine Immunol 15:1248-58
Basaraba, Randall J (2008) Experimental tuberculosis: the role of comparative pathology in the discovery of improved tuberculosis treatment strategies. Tuberculosis (Edinb) 88 Suppl 1:S35-47
Lenaerts, Anne J; Hoff, Donald; Aly, Sahar et al. (2007) Location of persisting mycobacteria in a Guinea pig model of tuberculosis revealed by r207910. Antimicrob Agents Chemother 51:3338-45
Hinchey, Joseph; Lee, Sunhee; Jeon, Bo Y et al. (2007) Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis. J Clin Invest 117:2279-88
Ordway, Diane; Palanisamy, Gopinath; Henao-Tamayo, Marcela et al. (2007) The cellular immune response to Mycobacterium tuberculosis infection in the guinea pig. J Immunol 179:2532-41
Basaraba, Randall J; Smith, Erin E; Shanley, Crystal A et al. (2006) Pulmonary lymphatics are primary sites of Mycobacterium tuberculosis infection in guinea pigs infected by aerosol. Infect Immun 74:5397-401
Basaraba, Randall J; Izzo, Angelo A; Brandt, Lise et al. (2006) Decreased survival of guinea pigs infected with Mycobacterium tuberculosis after multiple BCG vaccinations. Vaccine 24:280-6
Johnson, Christine M; Pandey, Rajesh; Sharma, Sadhna et al. (2005) Oral therapy using nanoparticle-encapsulated antituberculosis drugs in guinea pigs infected with Mycobacterium tuberculosis. Antimicrob Agents Chemother 49:4335-8

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