Evaluation of innovative TB vaccination strategies in preclinical and clinical models.

This proposal addresses some fundamental issues in TB vaccinology. In the absence of an immune correlate, there is a need for models with which we can evaluate the efficacy of new TB vaccines. The preclinical animal models have some utility; however, all of these preclinical models fail to represent the human situation in important ways. Currently, there is no gold standard which predicts efficacy in human clinical trials. This lack of reliable, relevant models with which to select which vaccin es should progress is the most significant challenge within the field of TB vaccine development today. The first aim in this proposal is to develop a human in-vivo mycobacterial challenge model with BCG. An effective vaccine against M.tb should also be effective against BCG. This model could subsequently be utilised to identify potential immunological correlates of protection. The second aim of this proposal is to evaluate new vaccination strategies in preclinical and early-stage clinical studie s. I will assess three ways in which our current vaccine, MVA85A, can be improved. First by addition of a second, potentially complementary recombinant viral vector; second, by using a potentially more protective route of immunisation, and third, by adding additional immunogenic antigens to the MVA85A construct.