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VACSIS


Tuberculosis (INCO)

Host-Parasite Relationship in Susceptibility to Tuberculosis
Framework programme:
5
Project number:
ICA4-CT-2002-10052
EC contribution:
€ 1 509 808
Duration:
36 months
Type:
RS
Starting date:
1 October 2001

Summary:

Vaccine candidates are emerging but the time and cost of TB clinical trials prohibits their evaluation. Surrogate markers are needed. Cells from carefully followed-up contacts who do or do not develop disease are being studied for cytokine expression by RT-PCR in three African centres. VACSIS will add a fourth centre, upgrade technology to real time RT-PCR, and study markers of apoptosis that play a role in immune response regulation in TB. Meanwhile, the patients’ TB strains will by typed for polymorphisms in DNA repair genes, and this will be related to disease severity, transmission and immunology.

Objectives:

The objective is to study blood mononuclear cells (and M. tuberculosis strains when available) from index cases and contacts who do or do not subsequently develop disease, and from community controls, in four genetically distinct African centres. With this material, the consortium will:

1) define markers of apoptosis associated with immunity to TB in unstimulated peripheral blood mononuclear cells and in cultures driven by a range of TB antigens in vitro

2) relate polymorphisms in DNA repair genes of the TB strains to disease severity, transmission and immune response

3) enhance the molecular immunology capacity of southern laboratories to enable them to adopt emerging technologies

4) encourage south-south collaboration of partner institutions

5) provide necessary immununological data, training and laboratory infrastructure for subsequent southern-led tuberculosis vaccine trials.

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