Though the bulk of deaths occur in developing countries, tuberculosis (TB) is an increasing global public health menace. No country is free of the disease, with incidences varying from 7/100,000 in Scandinavia to 300/100,000 in parts of Africa. In Eastern Europe the incidence has risen above 100/100,000 with a high incidence of multidrug resistant strains (up to 14% of the primary cases in Estonia). While chemotherapy has dramatically lowered the incidence of TB in countries with robust public health systems, other countries have witnessed no decrease in incidence, but instead an increase of antibiotic resistance. For these countries, vaccination remains the most cost effective intervention.

Both the potential and the problems of vaccination against TB are illustrated clearly by the experience with BCG, the only existing vaccine. When applied at birth or soon after, BCG protects children against severe TB (miliary TB and meningitis). However, BCG provides only minimal and inconsistent protection against the most common and infectious form of TB in adults, especially in TB-endemic areas. This applies to both reactivation of latent, previously acquired infection and new acute infection, and likely results from the waning of BCG induced immunity."

It is now thought that the primary reason for the lack of efficacy of the BCG vaccine is that it gives protection for only a limited period of time. Thus, current vaccination strategies are only effective in the short term against primary disease, and fail to activate immune responses that efficiently control M. tuberculosis in the longer term. However, in order to induce a significant degree of protection, BCG seems to require a period of multiplication in the host that is blocked in individuals with residual immunity, resulting from prior BCG vaccination or exposure to environmental mycobacteria. Demonstrated in animal models, this hypothesis can explain the failure of multiple BCG vaccination or adult vaccination in TB-endemic populations.

 

New improved vaccines are consequently needed to circumvent this problem and in particular for improving the immune status of the adolescent population in TB endemic areas.

 

 

TB-Vaccine cluster

The TB-Vaccine cluster was established during FP5. The cluster was composed of academic teams and industrial partners possessing complementary expertise, i.e. antigen discovery, structural biochemistry, immunology (human, and animals), animal models, genetics, genomics and vaccinology, and has significantly contributed to the integration and strengthening the European research area and its competitiveness in this field. The work has resulted in the development of several live and subunit vaccine candidates with improved efficacy (as compared to BCG) in various animal models. Importantly, unlike BCG, the efficacy of two subunit candidates is unimpaired by prior immunity to environmental mycobacteria in these animal models, and it is proposed that these will be further optimized and evaluated in the FP6 TB-VAC project. In addition to these new vaccine candidates, other discoveries were reported including new protein and non-protein antigens, new T cell populations, and new virulence factors, some of them being suspected of interfering with establishment of protective immune responses. In addition, standardisation of various animal models at dedicated institutes now allows good comparative evaluation of different vaccine candidates in different animal models.