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The T cell response to secreted antigens of Mycobacterium tuberculosis
1Statens Seruminstitute, Copenhagen, Denmark.
Abstract:
Recent information from several laboratories points to proteins secreted from live Mycobacterium tuberculosis as being involved in protective immunity. We have studied protein release from M. tuberculosis during growth and have defined 3 different groups of proteins: excreted proteins, secreted proteins of the outer cell wall and cytoplasmic proteins released at late culture timepoints. These findings have lead to the definition of a short-term culture filtrate (ST-CF) enriched in excreted/secreted proteins and with a minimal content of autolytic products. ST-CF was tested as antigen in experimental vaccines against tuberculosis. A vaccine based on the adjuvant dimethyldioctadecylammonium chloride (DDA) was constructed and demonstrated to induce a potent cell mediated immune response of the Th-1 type. The vaccine was tested in parallel with a BCG standard vaccine and both vaccines induced a highly significant protection of the same magnitude. Molecules within the Ag85 complex and a 6-kDA secreted protein were mapped as the major antigenic targets for long-lived T cells involved in protective immunity against M. tuberculosis.
Insights
Proteins secreted by Mycobacterium tuberculosis are key to protective immunity. A novel vaccine using short-term culture filtrate (ST-CF) induced significant protection against tuberculosis, comparable to BCG.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Protective immunity against tuberculosis is linked to proteins secreted by Mycobacterium tuberculosis.
- Understanding protein release during M. tuberculosis growth is crucial for vaccine development.
Purpose of the Study:
- To characterize protein release from M. tuberculosis.
- To develop and evaluate a novel vaccine candidate using short-term culture filtrate (ST-CF) as an antigen.
Main Methods:
- Categorization of M. tuberculosis proteins into excreted, secreted, and late-released cytoplasmic groups.
- Preparation of ST-CF enriched in excreted/secreted proteins.
- Immunization with ST-CF and dimethyldioctadecylammonium chloride (DDA) adjuvant in a vaccine model.
- Assessment of cell-mediated immune response (Th-1 type) and protection against tuberculosis challenge.
- Comparison with BCG standard vaccine.
Main Results:
- Defined three distinct protein release groups from M. tuberculosis.
- Developed ST-CF with minimal autolytic products, suitable as a vaccine antigen.
- The ST-CF/DDA vaccine induced a potent Th-1 cell-mediated immune response.
- Both ST-CF/DDA and BCG vaccines conferred significant and comparable protection against tuberculosis.
- Identified Ag85 complex molecules and a 6-kDa secreted protein as major antigenic targets for protective T cells.
Conclusions:
- Secreted proteins of M. tuberculosis are critical for inducing protective immunity.
- ST-CF is a promising antigen for developing effective tuberculosis vaccines.
- The ST-CF/DDA vaccine offers a viable alternative or adjunct to BCG vaccination.