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VACSEL


Tuberculosis (INCO)

Longitudinal Study of Correlates of Immunity to Tuberculosis in Exposed Individuals
Framework programme:
5
Project number:
ICA4-CT-1999-10005
EC contribution:
€ 1 280 000
Duration:
48 months
Type:
RS
Starting date:
1 January 2000

Summary:

Tuberculosis causes 2-3 million deaths each year. A more effective vaccine than BCG is required, but rational vaccine trials cannot be planned for two main reasons. Firstly, although many mycobacterial antigens have been isolated, it is not known which ones to test in human trials and it is not possible to test them all. Secondly, it is not known which mechanisms are crucial for killing M. tuberculosis in man, so an adjuvant cannot rationally be selected or short term pilot studies planned using surrogate markers of protection. VACSEL will, therefore, conduct longitudinal studies in three geographically distinct African countries of TB contacts who do or do not develop clinical disease, in order to identify the antigens, the cytokine profile and the markers of apoptosis that correlate with protection so that rational design and testing of vaccines can begin.

Objectives:

The overall objective is to acquire the information needed to allow the design of tuberculosis vaccines for trial in humans by the end of the project. This includes antigen selection, rates of transmission and identification of surrogate markers of protection so that volunteer studies can confirm the appropriateness of candidate vaccines before proceeding to large, lengthy protection studies. The specific objectives are:

1) to identify and follow cohorts of tuberculosis-exposed individuals in three geographically separate African countries

2) to transfer novel reagents and technology to these centres by training personnel

3) to identify antigens from M. tuberculosis recognised by T cells from exposed individuals who do and do not develop disease

4) to define cytokine profiles and markers of apoptosis associated with immunity in fresh, unstimulated, peripheral blood mononuclear cells, and in antigen-driven cultures.

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