We have identified several new TB vaccine candidate antigens based on human T cell responses and animal protection. Priority has been given to those that both elicit a Th1 response from PBMC from PPD positive healthy donors and protect in rodent models. Several animal models have been developed to evaluate vaccine efficacy and are currently being used to further characterize vaccine candidates and adjuvant/delivery systems. We propose to expand the evaluation of candidate vaccine antigens through extensive testing in clinically and geographically diverse populations, using state of the art immunological assays. This section will provide important information on conservation of antigens in genetically diverse populations infected with diverse isolates. These studies will also lay the foundation for definition of key immunological correlates of protection. In parallel, we will perform immunogenicity studies using priority antigens and vaccine formulations in rodent models. We will also perform detailed analysis of the immune responses of human volunteers immunized with Mtb72f in AS02A, the first defined TB vaccine to enter clinical trials. Finally, we will test antigens/vaccine formulations in rodent models of infection and disease. By the end of the funding period, we will have defined a second vaccine candidate for entry into clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044373-07
Application #
7056075
Study Section
Special Emphasis Panel (ZRG1-VMD (01))
Program Officer
Lacourciere, Karen A
Project Start
1999-09-30
Project End
2010-01-31
Budget Start
2006-02-01
Budget End
2007-01-31
Support Year
7
Fiscal Year
2006
Total Cost
$468,275
Indirect Cost
Name
Infectious Disease Research Institute
Department
Type
DUNS #
809846819
City
Seattle
State
WA
Country
United States
Zip Code
98102
Baldwin, Susan L; Reese, Valerie A; Huang, Po-Wei D et al. (2016) Protection and Long-Lived Immunity Induced by the ID93/GLA-SE Vaccine Candidate against a Clinical Mycobacterium tuberculosis Isolate. Clin Vaccine Immunol 23:137-47
Shanley, Crystal A; Ireton, Gregory C; Baldwin, Susan L et al. (2014) Therapeutic vaccination against relevant high virulence clinical isolates of Mycobacterium tuberculosis. Tuberculosis (Edinb) 94:140-7
Orr, Mark T; Ireton, Gregory C; Beebe, Elyse A et al. (2014) Immune subdominant antigens as vaccine candidates against Mycobacterium tuberculosis. J Immunol 193:2911-8
Baldwin, Susan L; Reese, Valerie; Granger, Brian et al. (2014) The ID93 tuberculosis vaccine candidate does not induce sensitivity to purified protein derivative. Clin Vaccine Immunol 21:1309-13
Jin, Jungho; Reese, Valerie; Coler, Rhea et al. (2014) Chitin microneedles for an easy-to-use tuberculosis skin test. Adv Healthc Mater 3:349-53
Jones, Gareth J; Steinbach, Sabine; Clifford, Derek et al. (2013) Immunisation with ID83 fusion protein induces antigen-specific cell mediated and humoral immune responses in cattle. Vaccine 31:5250-5
Orr, Mark T; Fox, Christopher B; Baldwin, Susan L et al. (2013) Adjuvant formulation structure and composition are critical for the development of an effective vaccine against tuberculosis. J Control Release 172:190-200
Coler, Rhea N; Bertholet, Sylvie; Pine, Samuel O et al. (2013) Therapeutic immunization against Mycobacterium tuberculosis is an effective adjunct to antibiotic treatment. J Infect Dis 207:1242-52
Vernatter, Joshua; Pirofski, Liise-anne (2013) Current concepts in host-microbe interaction leading to pneumococcal pneumonia. Curr Opin Infect Dis 26:277-83
Baldwin, Susan L; Ching, Lance K; Pine, Samuel O et al. (2013) Protection against tuberculosis with homologous or heterologous protein/vector vaccine approaches is not dependent on CD8+ T cells. J Immunol 191:2514-2525

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