MUCOSAL TB VACCINE

Framework programme:

5

Project number:

QLK2-CT-1999-00367

EC contribution:

€ 1 078 845

Duration:

36 months

Type:

RS

Starting date:

1 February 2000

Keywords: Tuberculosis; mucosal immunity; mucosal vaccination; T-cell immunology; vaccine

Summary:

Tuberculosis (TB) is a re-emerging disease, and has been designated a ‘global health emergency’ by the World Health Organisation. The current vaccine (BCG) is not fully effective, and so there is a need to develop a more effective vaccine. The aim of the project is to determine whether an improved vaccine against TB can be designed by inducing mucosal immunity directly in the lung. The project involves collaboration between microbiologists and immunologists to develop new vaccine candidates and novel routes of delivery to achieve enhanced protection in the lung.

Problem:

Over recent years, TB has re-emerged as one of the leading causes of death (nearly 3 million die annually). In humans, the main cause of TB is infection following inhalation of the intracellular pathogen, Mycobacterium tuberculosis. Some of these strains are now resistant to a number of front-line antibiotics. Vaccination is one approach to control this disease. However, the current vaccine (BCG) does not protect all age groups, its efficacy is globally variable, and it does not provide protection in many Third World countries where TB is prevalent. BCG is also a live vaccine, and is not suitable for use with immuno-compromised patients. In addition, BCG reduces dissemination of M. tuberculosis to the spleen and other organs, but does not prevent mycobacterial growth in the lungs. Therefore, an improved vaccine is required.

Previous and current attempts to produce a more effective vaccine have been generally focused on inducing a cell-mediated immune response to kill the intracellular bacilli. So far, however, these approaches have not produced a vaccine that has induced protection significantly better than BCG, suggesting that a more novel vaccine strategy is required. As an example, it has been demonstrated recently that mucosal antibodies (particularly IgA) can inhibit the growth of intracellular pathogens. These and other findings are being applied in these studies to develop a more effective TB vaccine.