Lyophilization of Plasmodium falciparum sporozoite vaccine

DESCRIPTION (provided by applicant): Malaria causes 500 million clinical cases and 1-3 million deaths annually, is responsible for a loss of > 1% of GDP in Africa annually, and is a serious concern for travelers and military personnel. When attenuated Plasmodium falciparum sporozoites (PfSPZ) are administered by bite of infected mosquitoes > 90% of human volunteers 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 3 markets with a potential for > $1 billion annual revenues; 1) Travelers from the developed world, 2) Infants and young children in the developing world, and 3) Adolescent girls in the developing world. In a separate Phase II SBIR we are developing the prototype, a PfSPZ vaccine using the NF54 strain of Pf using cryopreservation as the method of storage of the live attenuated sporozoites. The cryopreservation protocol produces high yields of viable PfSPZ which are banked under vapor phase nitrogen storage at below -135xC. The development of a storage protocol that utilizes lyophilization would produce a considerable benefit to storage of the vaccine and to the logistics of its delivery. Lyophilization is a process commonly used to store non-living vaccines, and which is also in routine use for the storage of stock strains of many prokaryotes and also certain protozoa. In preliminary studies, PfSPZ tolerate lyoprotective agents well, including those agents commonly used in the lyophilization of other commercial injectable products, and PfSPZ can be cryopreserved successfully using these compounds as cryoprotective agents. The goal of this proposal is to develop a lyophilization method for live attenuated PfSPZ that can be scaled up for large scale manufacturing, storage and distribution of the live attenuated PfSPZ vaccine. The in vitro assay that we use to validate and quantify the potency of the prototype attenuated PfSPZ vaccine will be used to demonstrate that lyophilized PfSPZ are viable. This is done by demonstrating that the lyophilized and reconstituted PfSPZ are able to invade human hepatocytes and express proteins in the hepatocytes that are not expressed in sporozoites. In a Phase II SBIR and subsequent studies we will incorporate the lyophilization method for the storage of live, attenuated PfSPz into the cGMP manufacturing process for the vaccine, and assess the safety, immunogenicity and protective efficacy of the lyophilized PfSPZ vaccine in clinical trials. 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. An effective vaccine against Plasmodium falciparum malaria will fundamentally alter the cycle of poverty and illness and will accelerate economic investment into Africa and other afflicted areas. We have demonstrated that a frozen attenuated-parasite vaccine has unprecedented protective efficacy and potential. However, a vaccine that has been dried and does not require refrigeration would allow the vaccine to be more easily produced, transported and stored. A dried vaccine promises to reduce the cost of the vaccine which is an important economic factor when producing millions of vaccine doses for at risk populations. Additionally, a dried vaccine may accelerate a concerted world-wide effort to eradicate this devastating disease.