Objective
Tuberculosis (TB) is a global health problem which causes 3 million deaths yearly. In industrialized countries, the incidence of the disease is rising because of the AIDS epidemic and immigration from developing countries. The available vaccine, Mycobacterium bovis bacillus Calmette-Guerin, is of questionable efficacy, therefore the development of a subunit vaccine is needed. The project proposed aims at identifying immunodominant antigens as candidate components of such a vaccine, with a special focus on proteins secreted by mycobacteria during growth in vitro or produced intracellularly. It has been shown that immune CD4+T cells play a key role in immunity to M. tuberculosis in animal models. Other cell populations (natural killer cells, CD8+ and gammadelta+ T cells) also seem to be involved. Although there is evidence that T cell immunity is essential to recover from human infection too, the antigens responsible for its induction and the role of each T cell subset are still unclear. The project proposed aims at: 1) identifying M. tuberculosis, M. av um or BCG antigens involved in protective immunity. This would proceed by isolating sets of mycobacterial proteins produced in vitro (membrane, cytosol, cell wall and secretory fractions) and in vivo, inside cells, and investigating their ability to induce proliferation of human immune lymphocytes in vitro and/or release of cytokines.
The final goal of this phase would be to molecularly clone them from a DNA expression library to test whether they might induce, a10ne or in combination, an immune status against M. tuberculosis in mice. 2) Dissection of human immune Iymphocyte proliferation to mycobacterial antigen fractions in vitro. The response of peripheral blood mononuclear cells from different human subjects (BCG-vaccinated or unvaccinated PPD+, PPD-, HIV+ and HIVtuberculous individuals) will be analyzed: i) to assess whether alfabeta+, gammadelta+ T cells or natural killer cells are mostly responsible for proliferation to the antigen fractions of choice or to cloned proteins, and whether a particular antigen is capable of inducing the release of interferon y or other immunologically relevant lymphokines; ii) to assess whether the reduction of CD4+ T cells in HIV+ patients is compensated by other lymphocyte subsets; iii) to determine whether any carbohydrate antigen accounts for proliferation of natural killer or gammadelta+ T cells. 3) Study of a rapid method for early detection of mycobacterial infection. A new method based on detection of lipoarabinomannan in urine will be set up and evaluated for the diagnosis of mycobacterial infection in HIV+ and HIV- tuberculous patients and for its ability to detect infection before active disease develops. The method will be also evaluated by monitoring infection in experimental animals
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences health sciences infectious diseases RNA viruses HIV
- medical and health sciences clinical medicine pneumology tuberculosis
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
- social sciences sociology demography human migrations
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
56100 Pisa
Italy
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.