SBIR-STTR Award

Plasmodium falciparum malaria infects 5-10% of the global population (400 million clinical cases) and kills two million people annually. As such it ranks along with HIV and TB as the most serious infectious disease of humanity. It is widely accepted that an efficacious vaccine is required to afford protection against malarial fatalities. Recent research demonstrates the feasibility of a carbohydrate molecule-based Malaria vaccine approach. Scientific evidence shows that a glycosylphosphatidylinositol (GPI) molecule, a glycolipid-related carbohydrate, of Malarial parasite origin utilized as a vaccine can prevent the pathology and fatalities in rodent models of severe malaria. Three critical parameters to be considered in the generation of the optimal Malaria Vaccine molecule include: the identification of the minimal immunogenic molecule sequence that determines the specificity of immune response; the capability to generate sufficient material quantities for the requisite pre-clinical trials; and, the appropriate protein conjugate and adjuvant to potentiate the immune response. The goal of this SBIR proposal is to develop the synthesis strategy for large-scale molecule preparation and to generate a set of vaccine molecules that will help elucidate the lead vaccine molecule for subsequent advanced pre-clinical trials.

Thesaurus Terms:
drug delivery system, malaria vaccine, vaccine development carbohydrate, glycosylphosphatidylinositol, protein

Malarial disease represents one of the most pressing medical healthcare issues facing the world today. While limited drug treatment options exist, a vaccine solution is widely considered as one of the most effective therapeutic weapons to combat malaria. Despite years of research, though, malarial vaccine initiatives have yet to produce a viable candidate. One vaccine candidate continues to show potential: the anti-toxin malaria vaccine. This approach directs the immune response against the carbohydrate portion of the malaria toxin, glycophosphotidyl inositol (GPI), a glycolipid. Given the significant advances in GPI carbohydrate synthesis supported by a Phase I SBIR, a drug development path for the malarial GPI vaccine candidate can now be proposed and executed. To develop the vaccine candidate the following objectives will be addressed: 1. Synthesis and characterization of multigram quantities of GPI antigen molecule. This will be performed utilizing the protocols developed during the Phase I SBIR. 2. Preliminary efficacy and safety studies. The vaccine candidate will be evaluated for efficacy in a rodent model of cerebral malaria and in two species safety. 3. Establishment of analytical and synthesis processes to enable drug substance generation. The synthesis process will be optimized and analytical methods will be developed to facilitate reliable, large-scale vaccine generation 4. Efficacy evaluation in a primate model. Vaccine candidates will be tested in a primate malarial model system for their ability to prevent cytokine cascade and anemia. 5. Pre-Good Laboratory Practices (GLP) drug substance evaluation. The drug substance and synthetic process will be characterized fully. Multigram pilot batches of material will be produced and analyzed The goal is to establish the final process development path that will generate the formal data and protocols required to enable an investigational new drug (IND) application for the malarial GPI vaccine candidate