Malaria causes 500 million clinical cases &1-3 million deaths/yr, is responsible for >1% loss of GDP in Africa/yr, and is a serious concern for travelers. When attenuated P. falciparum sporozoites (PfSPZ) are administered by bite of infected mosquitoes >90% of humans are protected against experimental Pf challenge and protection lasts at least 10.5 months. Sanaria's goal is to develop and commercialize a >90% protective attenuated PfSPZ vaccine for primary markets with potential for >$1 billion revenues/yr;1) Travelers from the developed world, and 2) Infants, children, &adolescent girls in the developing world. In a separate Phase II SBIR we are developing the prototype, a PfSPZ vaccine using NF54 isolate of Pf. Because of variability of Pf at B &T cell epitopes, optimal development will require, 1) Assessment of protection against multiple isolates of Pf in experimentally challenged volunteers and the field, and 2) Capacity to produce a universally effective vaccine by mixing different isolates of PfSPZ to reduce or eliminate potential negative effects of antigenic diversity on vaccine efficacy. Building on a Phase 1 SBIR this project will establish 3 new isolates of Pf to assess protection in volunteers immunized with NF54-based PfSPZ vaccine, and, if necessary, be included in a multi-strain PfSPZ vaccine. We will, 1) Produce infective PfSPZ from 3 isolates of Pf from different geographic origins than Pf NF54, 2) Establish and store Master (MCB) and Working (WCB) Cell Banks of the 3 Pf isolates and store them under current Good Manufacturing Practices, 3) Produce aseptic mosquitoes infected with PfSPZ derived from the WCB of each isolate, 4) Obtain aseptically dissected, extracted, purified, and cryopreserved PfSPZ from each isolate, 5) Establish that PfSPZ (from 3 above) from each isolate invade and develops normally in a human hepatocyte cell line clone, 6) Submit to FDA addenda to the Biologics Master File on the aseptic NF54 challenge system for each isolate, 7) Submit addenda for the 3 new Pf isolates to the investigational new drug application (IND) for the NF54 aseptic infected mosquito challenge NIAID is submitting in collaboration with Sanaria. In Phase III we will assess the NF54 PfSPZ vaccine in volunteers challenged by bite of mosquitoes infected with NF54 and the 3 new isolates and in Ghana. We will also develop a system of challenging volunteers by injection of aseptic, purified, vialed, cryopreserved PfSPZ of all 4 isolates, creating the capacity for investigators worldwide to conduct PfSPZ challenge studies. Establishing 3 new Pf isolates will decrease the time and cost to receive a license (BLA) from FDA for the PfSPZ vaccine. Malaria causes 500 million clinical cases and 1-3 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 primary markets with a potential for >$1 billion annual revenues;1) Travelers from the developed world, and 2) Infants, young children, and adolescent girls in the developing world. Success in this project will significantly decrease the cost of development and time to market for this malaria vaccine.
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