This proposal is designed to identify, characterize, and clone Mycobacterium tuberculosis genes encoding proteins associated with specific T cell responses of presumed protected humans and animals. Antigens associated with both CD4+ and/or CD8+ T cell responses are the target of this proposal. The recent identification, by our group, of a novel and protective antigen opens new possibilities for vaccine development. Two other antigens/gene have been cloned, expressed, and purified. They will be evaluated for their ability to elicit T cell responses from human PBMC, primarily from non-BCG immunized PPD+ healthy individuals. The recombinant antigens alone and in combination will also be evaluated as vaccine candidates in three animal protection models, including mice, guinea pigs, and cynomolgus monkeys, all of which will be challenged by aerosol or intratracheal routes. In addition to the evaluation of these antigens, we will characterize and clone other vaccine candidates using recently developed approaches for the direct identification of both CD4 and CD8 T cell antigens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI043528-02
Application #
6373901
Study Section
Special Emphasis Panel (ZRG1-VACC (01))
Program Officer
Sizemore, Christine F
Project Start
2000-09-01
Project End
2005-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$293,446
Indirect Cost
Name
Infectious Disease Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98102
Coler, R N; Campos-Neto, A; Ovendale, P et al. (2001) Vaccination with the T cell antigen Mtb 8.4 protects against challenge with Mycobacterium tuberculosis. J Immunol 166:6227-35