Improved vaccines against tuberculosis based on dendritic cell manipulation [ 2001 - 2003 ]

Research Grant

Researchers: Prof Warwick Britton (Principal investigator) ,  Dr Caroline Demangel ,  Helen Briscoe

Brief description The incidence of tuberculosis (TB) is increasing throughout the world. BCG, the only currently available vaccine is only partially protective and better vaccines are urgently required to help limit the spread of TB. We have recently prepared naked DNA vaccines with the genes for three mycobacterial proteins and found that they partially protected against lung TB in mice. Further improvement is required and this project is to design and test improved DNA vaccines. Vaccines will be more effective if they generate stronger cellular immune response to mycobacteria. Dendritic cells (DC) are the major cells that present mycobacterial antigens to T lymphocytes and thus stimulate T lymphocytes to generate immune responses that protect against TB. Therefore the aim of this project is to identify ways to manipulate DC to improve their ability to activate protective immunity. We will target membrane molecules on DC to activate the antigen- presenting function of these cells by fusing the genes for mycobacterial proteins to genes either for antibodies to surface molecules on DC or receptors for these molecules. These novel DNA vaccines will be tested for their effects on DC function and their capacity to stimulate the protective pattern of immunity in mice. The cytokine environment at the time of stimulation will be modified by giving the DNA vaccine together with two cytokine-expressing vaccines, to 'push' the T lymphocytes to respond more vigorously. Finally, we shall test whether a combination of the new DNA vaccines and BCG is more effective than BCG at protecting against virulent TB infection.

Funding Amount $AUD 257,036.72

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant