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Identification of mycobacterial antigens as candidates for a subunit vaccine against tuberculosis in healthy and HIV infected individuals

Objective

-To produce large standardized quantities of mycobacterial antigenic fractions.
-To identify and clone new mycobacterial antigens and test them as antimycobacterial subunit vaccines in the mouse.
-To determine the response of defined human lymphocyte subsets from healthy and tuberculous patients with or without AIDS.
-To characterize carbohydrate antigens for NK or xdelta+ T cells and their receptors.
-To test the efficacy of a new diagnostic method on urine from adults with mycobacterial infection.

Tuberculosis is a global health problem which causes 3 million deaths yearly. The available vaccine, Mycobacterium bovis bacillus Calmette-Guérin, 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. Sets of mycobacterial proteins produced in vitro (membrane, cytosol, cell wall and secretory fractions) and intracellularly, will be isolated and studied for their ability to induce proliferation of human immune lymphocytes in vitro and/or release of cytokines. The recombinant antigens will be tested as to whether they induce an immune status against M. tuberculosis in mice. Moreover, the response of peripheral blood mononuclear cells from human subjects (BCG-vaccinated or unvaccinated PPD+, PPD-, HIV+ and HIV- tuberculous individuals) will be analyzed to assess whether xbeta+, xdelta+ T cells or natural killer cells are mostly responsible for proliferation to the antigen fractions of choice or to cloned proteins and to determine whether any carbohydrate antigen accounts for proliferation of natural killer or xdelta+ T cells. A new method based on detection of lipoarabinomannan in urine will be evaluated for the diagnosis of mycobacterial infection in HIV+ and HIV- tuberculous patients and for its ability to detect infection before active disease develops.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

Università degli Studi di Pisa
Address
Via San Zeno 35-39
56100 Pisa
Italy

Participants (5)

Institute of Microbiology
Czechia
Address
1083,Videnska 1083
14220 Prague
Karolinska Institute
Sweden
Address
13,Doktorsringen 13
171 77 Stockholm
St George's Hospital Medical School
United Kingdom
Address
Jenner Wing
London
Universidade do Porto
Portugal
Address
2,Largo Abel Salazar 2
4050 Porto
Uppsala University
Sweden
Address
583,Bio Centre Box
75123 Uppsala