Optimization of a Multivalent Tuberculosis Vaccine

DESCRIPTION (provided by applicant): This new Phase I SBIR proposal addresses the continuing worldwide need for a tuberculosis (TB) vaccine. We detail a novel multivalent strategy that aims to elicit immunity to prevent reactivation of latent TB. This epitope-driven, DNA-prime, protein-boost TB vaccine has been in development since 1997, when our immunoinformatics tools were first applied to identify T cell epitopes from TB proteins. In progress made during the three years of NIH and Sequella/Aeras TB Foundation support, we completed mapping of three sets of TB epitopes including novel epitopes predicted directly from the TB CDC1551 genome. In the next phase of the research program, building on our own experiences and our collaborations, we seek to develop the optimal vaccination strategy, using HLA transgenic mice as the model for in vivo study. Before the start of the performance period, we will make the final epitope selections. In the course of the SBIR award period, selected epitopes will be formulated as DNA and peptide/protein vaccines. By means of a prime-boost vaccination strategy, we will optimize key vaccination parameters (administration route, antigen targeting, adjuvant) to induce the greatest immunogenicity as assessed by cytokine production of stimulated immune cells. Next, we will determine the protective efficacy of the optimized TB vaccine against the standard bacilli Calmette-Gurin (BCG) vaccine and as a boost in HLA transgenic mice pre-vaccinated with BCG. Successful completion of this work will set the stage for Phase II development that will partner the vaccine with improved recombinant BCG vaccines and assess efficacy in additional strains of HLA transgenic mice.