Developing vaccines against the intracellular and extracellular Lifestages of the Cryptosporidium parasite

Project Summary Introduction: The goal of this work is to develop a vaccine against cryptosporidiosis. No vaccine exists to prevent cryptosporidiosis which remains a common cause of diarrheal disease in sub-Saharan Africa and Asia. It is a particular problem in young children who in general only develop immunity to this parasite after repeated infections. Hypothesis: This apicomplexan parasite has a complex life cycle and a vaccine that targets a combination of parasitic life-stages would be the most effective defense. Significance: Cryptosporidium causes 7 million cases of diarrhea, 200,000 deaths per annum, and the loss of 12 million disability-adjusted life-years. It also exacerbates the growth faltering in children living in food- insecure households. Investigators: A longstanding collaboration exists between Drs. Petri, Abhyankar & Gilchrist at the University of Virginia and Dr. Fox at AAHI. This has already identified parasite antigens associated with immunity, and already demonstrated the immunogenicity of the liposomal vaccine formulation we plan to use in non-human primates. Innovation: This application utilizes a novel liposomal vaccine formulation incorporating toll-like receptor agonists that stimulate both cellular and humoral immunity. This work is also novel in that we are testing targets from both the extracellular and intracellular life stages of the parasite Approach: Specific Aim 1. Optimize the systemic and cellular immune responses in prototype vaccines for Cp17, Cp23 & CpSMP. A prioritization scoring matrix will be used that incorporates the information on the mucosal and systemic immune responses to identify the most promising candidates for Aim 2. Specific Aim2 : Determine the Protective efficacy of the optimal vaccine formulation. Using the mouse model of cryptosporidiosis the ability of the vaccine combination identified in Aim 1 to protect against cryptosporidiosis will be tested. Environment: The University of Virginia is internationally recognized as a center for Global Health research, the icddr,b is the premier institution for the study of diarrheal diseases in low and middle income countries.