Nanoparticle Based Tuberculosis Vaccine
Tuberculosis (TB) is a growing world health problem, especially in developing countries. The only available vaccine is the hundred years old Bacille de Calmette et Guérin (BCG). It has been shown to reduce infant mortality, but it is not an effective method for preventing TB in adults. A new vaccine that can safely and effectively be administered in infancy and confers long-term protection against TB is urgently needed. Using a novel nanoparticle (NP) delivery platform developed in the laboratories of Prof. Swartz and Prof. Hubbell at the Swiss Federal Institute of Technology in Lausanne (EPFL), we are proposing a research plan for the development of a TB vaccine. The NP platform has been shown to be extremely stable, safe, cheap, and able to induce strong T-cell responses, and thus we expect it has potential to be an effective vaccine that holds advantages over the current candidates. We describe a preclinical testing plan that includes best formulation selection, dosage determination, efficacy, and safety testing. We also explored manufacturing process, regulatory issues, and the transition to clinical trials. This part of the project was done in Cape Town as part of a MS Honor Program in Bioengineering for Global Health 2008, and it reflects the work of Jamie Carter (Northwestern University), Garrett Green (Northwestern University), Bastien Schyrr (EPFL), Alexandre de Titta (EPFL) and myself. Before we can couple a TB antigen to the NPs, the basics of this vaccine platform behavior need to be explored. My research in Prof. Swartz's laboratory (EPFL) on the characterization of uptake and processing of NPs by dendritic cells (DCs) will be presented. This is key since the immune response relies on the way the antigen is uptaken and processed. Data suggesting caveolin dependent uptake, presence of NPs in the cytoplasm, and presentation via MHC class I and MHC class II molecules was collected by a set of immunofluorescence experiments on mice DCs.