DESCRIPTION (provided by applicant): Sanaria was founded in 2003 to develop and commercialize an attenuated sporozoite Plasmodium falciparum (Pf) (PfSPZ) vaccine against malaria. Since then Sanaria has established a manufacturing process, manufactured the PfSPZ Vaccine under cGMPs, submitted an investigational new drug application (IND) to the FDA, received clearance from the FDA to proceed to clinical trials, and initiated the first Phase 1 clinical trial to assess safety, immunogenicity, and protective efficacy of SANARIA PfSPZ Vaccine in May 2009. The PfSPZ vaccine is comprised of Pf sporozoites extracted from infected mosquitoes and a short term challenge for Sanaria involves the optimization of this extraction step in its manufacturing process. Currently, human operators manually carry out the critical task of isolating the sporozoites by serially dissecting salivary glands from individual mosquitoes. Sanaria has established this procedure as a reliable, reproducible, consistent, and efficient process. In the next phase of development, as we optimize the efficiency and expand the scale of vaccine manufacturing, automation of mosquito dissection will prove to be beneficial on several fronts. It will enable us to cut the costs of supporting a large taskforce of skilled technicians, the time taken to train and qualify them and the dedicated space necessary for a scaled-up manual operation. Therefore in this SBIR proposal, we focus on successfully developing strategies to mechanize the process of dissection and collection of mosquito salivary glands. In collaboration with the School of Engineering and Applied Sciences at Harvard University we propose to develop novel instrumentation and innovative technologies to meet this goal. These will be addressed in three specific aims in which we will develop procedures that will allow batch processing of mosquitoes to isolate intact salivary glands with minimal manual involvement. This will be achieved using mechanical engineering and physical chemistry principles. First, in specific aim 1 we will create ordered arrays of mosquitoes and in specific aim 2 we will develop methods to decapitate mosquitoes and to extract and collect the salivary glands without losing sporozoites. The technology described here is expected to achieve very high throughput and process scalability. In specific aim 3 we propose a direct substitution of our current dissection configuration with robotic arms and vision guided microscope systems. This serial processing approach will circumvent the need to create mosquito assemblies and involves limited, if any, manual operation. The end-product from the advanced automated techniques however must match or exceed Sanaria's current standards for vaccine yield and potency and will drive the decision to translate our current method of mosquito salivary gland dissection to an automated platform. PUBLIC HEALTH RELEVANCE: Malaria causes >300 million clinical cases and 1 million deaths annually, is responsible for >1% loss of GDP in Africa annually and is a serious concern for travelers and military personnel. Sanaria's goal is to develop and commercialize a >90% protective malaria vaccine for three primary markets with a potential for >$1 billion annual revenues: 1) Travelers from the developed world to malaria endemic areas. 2) Infants and young children in the developing world. 3) Adolescent girls in the developing world. Success in this Phase I SBIR will lead to a significant increase in the efficiency of manufacture of the PfSPZ Vaccine that will facilitate scale-up of manufacturing and significantly reduce the cost of goods.

PROJECT NARRATIVE Malaria causes >300 million clinical cases and 1 million deaths annually, is responsible for >1% loss of GDP in Africa annually and is a serious concern for travelers and military personnel. Sanaria's goal is to develop and commercialize a >90% protective malaria vaccine for three primary markets with a potential for >$1 billion annual revenues: 1) Travelers from the developed world to malaria endemic areas. 2) Infants and young children in the developing world. 3) Adolescent girls in the developing world. Success in this Phase I SBIR will lead to a significant increase in the efficiency of manufacture of the PfSPZ Vaccine that will facilitate scale-up of manufacturing and significantly reduce the cost of goods.