Abstract

This proposal is aimed at identifying and characterizing T cell antigens of M. tuberculosis which may be important vaccine candidates. To identify novel Mtb antigens which may be relevant in protective immunity against tuberculosis we have used a variety of antigen discovery methods which emphasize expression cloning with anti-M. tuberculosis antisera and human T cells. Eight vaccine candidates (Mtb 8.4, Mtb 9.8, Mtb 9.9, Mtb 11, Mtb 19, Mtb 32, Mtb 39, Mtb 40) have so far been selected based on their ability to stimulate PBMC from donors infected with M. tuberculosis. These eight antigen genes will be evaluated as recombinant antigens or as naked DNA, alone or in combination, for immunogenicity and protection against tuberculosis in three animal models including cynomolgus monkeys, mice, and guinea pigs. These models will be used to assess T cell responses as well as protection. In addition, we will emphasize the use of human T cell expression cloning to identify other vaccine candidate antigens. These will be characterized in the in vitro and animal models as above.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI044373-04
Application #
6534130
Study Section
Special Emphasis Panel (ZRG1-BM-1 (03))
Program Officer
Sizemore, Christine F
Project Start
1999-09-30
Project End
2004-06-30
Budget Start
2002-09-01
Budget End
2003-06-30
Support Year
4
Fiscal Year
2002
Total Cost
$332,888
Indirect Cost

  Institution

Name
Infectious Disease Research Institute
Department
Type
DUNS #
City
Seattle
State
WA
Country
United States
Zip Code
98102

  Publications

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
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
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

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