The major objective of the TB-VAC project is to identify, develop and evaluate in preclinical and clinical Phase I trials new and improved vaccines that will:

1. Offer effective protection in the adolescent population particularly in TB-endemic countries
2. Not be impaired by prior immunity to environmental mycobacteria
3. Be at least safe, and preferably effective in HIV-positive populations (as a significant proportion of the population of the TB-endemic areas are likely to be HIV-positive)

TB-VAC aims to continue to build on the experiences and discoveries made in the TB-Vaccine cluster. Whereas preclinical vaccine discovery and development was the main focus of the TB-Vaccine cluster, TB-VAC proposes a three component approach that includes Phase I clinical trials:

Vaccine discovery

To identify and develop novel vaccines or antigen components:

with many mycobacterial genomes (including M. tuberculosis) and the human genome available, global genome, gene-expression and proteome profiling technologies will be applied in innovative strategies to identify new vaccines and antigens extending the limited number of promising candidate vaccines developed during FP5

Strategic research

To optimize the delivery and composition and to evaluate safety, immunogenicity, and protective efficacy of a selected number of promising candidate vaccines in relevant animal models.

This will allow selection of a second generation of vaccine candidates for further evaluation and downstream development in clinical trials § To identify and develop human correlates of protection and markers of TB disease and TB immunopathology. Development of these correlates forms an essential part of TB-VAC as their availability will have a profound impact on the time and resources needed for evaluation of vaccine candidates in future clinical trials and early identification of the most effective vaccines.

Downstream development

To carry out GMP production, regulatory aspects of vaccine development and Phase I clinical trials, including trials in TB-endemic areas

An initial broad effort including an important vaccine discovery component is proposed in order to avoid the risk of failure at the clinical trials phase by focusing only on the very limited number of vaccine candidates available (essentially only those identified during FP5).

After two years, therefore, TB-VAC will select the most promising vaccine candidates, and mainly focus its resources (with the attraction of appropriate new partners) on the activities in the strategic and downstream development component.

Another objective of TB-VAC is to continue strengthening collaborative research capacity within the European Research Area in the field of tuberculosis.

To achieve these objectives, TB-VAC will bring together several groups, SMEs and a major pharmaceutical company with complementary state-of-the-art global high throughput technologies. The TB-VAC partners will also share expertise to overcome some of the technological and bio-informatic obstacles that still hamper the interpretation of global patterns obtained with these technologies.

The project brings together several new groups with novel delivery systems and immunomodulatory adjutants that will promote development of more effective ways to induce prolonged memory for effective protection, while decreasing the induction of pathological effects as compared to current systems. Thus, researchers in the area of glycolipid biochemistry will be joined with immunologists and cell biologists to identify immunomodulatory molecules affecting receptors and functions of dendritic and other antigen presenting cells that result in the activation and stimulation of a variety of conventional and non-conventional T cells. Genetic inactivation of the responsible genes for these immunomodulators in BCG may contribute to the development of live vaccines with improved protective or decreased pathological effects.