Research Project
10109966
ABSTRACT: PfSPZ Vaccine is currently on track to be the world?s first licensed vaccine against malaria and the first vaccine against a human parasitic disease. PfSPZ Vaccine is composed of aseptic, attenuated, metabolically active, purified, vialed and cryopreserved Plasmodium falciparum (Pf) sporozoites (SPZ). Manufacture of PfSPZ Vaccine shares all steps (except radiation attenuation) with PfSPZ Challenge that is used by researchers worldwide in controlled human malaria infections to evaluate experimental malaria drugs, candidate vaccines, and natural immunity or resistance to malaria. The third product under clinical testing is PfSPZ-CVac, PfSPZ Challenge given under chemoprophylactic cover. PfSPZ Vaccine has protected against homologous (same strain) and heterologous (different strains) of Plasmodium falciparum (Pf) malaria in clinical trials conducted in the U.S., Germany, Tanzania, and Mali. To date, 80?100% protection lasting for at least 8 months against heterologous and 14 months against homologous challenge infections has been demonstrated. Ongoing trials in Gabon, Mali, and Equatorial Guinea are testing optimized regimens in preparation for Phase 3 clinical trials starting in 2020 in support of a Biologics License Application (BLA) to the FDA in 2021. All PfSPZ products are produced in mosquitoes reared aseptically from disinfected eggs that are harvested from a continuously-maintained Anopheles stephensi colony. The goals of this project are to submit a Biologics Master File for Sanaria?s cryopreserved A. stephensi SDA500 strain in support of the manufacture of PfSPZ- based products and to manufacture one lot of PfSPZ Challenge using mosquitoes derived from cryopreserved eggs, and also to adapt the methodology for large scale cryopreservation of A. gambiae. Fundamental to this process is the elevation of mosquito production from banks of cryopreserved eggs at full cGMP compliance. The work will involve cryopreservation of eggs at hugely increased scale and the generation of a master egg bank (MEB) and working egg bank (WEB) of cryopreserved A. stephensi SDA500 eggs. The work is incorporated into three specific aims: 1) Complete the GMP-compliant manufacture of a MEB and WEB which will entail development of novel release and stability assays, generation of SOPs and Certificates of Analysis, establishment of a stability program for cryopreserved eggs and submission of a Biologics Master File to the FDA; 2) Manufacture, using mosquitoes derived from the cryopreserved WEB, one lot of PfSPZ Challenge for use in clinical trials; and 3) Cryopreserve A. gambiae eggs at scale to support mosquito release programs. Cryopreservation of Anopheles eggs is a breakthrough enabling technology that will be available to support Anopheles mosquito research, particularly in laboratories that need to retain genetically modified strains and lines but have limited resources to do so.
