Manufacture of aseptic purified cryopreserved Plasmodium vivax sporozoites PvSPZ Challenge for controlled human malaria infection CHMI

DESCRIPTION provided by applicant Plasmodium vivax Pv the second most important human malaria parasite causes more than million cases annually including severe fatal disease Prevention and control are challenged by emerging drug resistance and relapses from dormant liver stage parasites called hypnozoites The only therapy against relapse primaquine causes life threatening acute hemolytic anemia in patients with G PD deficiency the most prevalent human genetic disorder affecting of people in malaria endemic nations This barrier to treatment results in repeated Pv attacks aggravating the problem of control The demonstration of high level long lasting at least months protective efficacy of Sanariaandapos s sporozoite SPZ based vaccines against Pf malaria is a significant milestone and indicates that such vaccines will constitute a viable approach to containing and eliminating Pf We believe that the same vaccine approach could work for Pv In the development of the Pf vaccines controlled human malaria infection CHMI has been an engine of progress accelerating the testing of vaccine candidates Pf CHMI has recently been revolutionized by the development of Sanariaandapos s PfSPZ Challenge aseptic purified cryopreserved fully infectious PfSPZ derived from in vitro cultures of Pf gametocytes enabling the successful infection of volunteers by intradermal intramuscular and intravenous injection in countries in Africa and countries in Europe that had never conducted CHMI before In contrast development of Pv SPZ based products has suffered from lack of available technology to culture Pv parasites in vitro such that generating infected mosquitoes for CHMI required membrane feeding on fresh Pv infected blood from Pv patients We have now overcome this major limitation by using Pv gametocyte infected Saimiri boliviensis non human primates NHPs to produce PvSPZ In fact we are the only laboratory with an inventory of vialed PvSPZ made from NHP infected blood having produced as much as million PvSPZ vialed in day from mosquitoes These cryopreserved PvSPZ are infectious to hepatocyte cell lines in vitro in traditional monolayer formats over days and in micro patterned co cultured primary human hepatocytes over days and infectious to NHPs in vivo We now propose to produce aseptic purified cryopreserved infectious PvSPZ PvSPZ Challenge by using a specific germ free colony of the permissive S boliviensis as the source for Pv infected blood This novel pipeline will generate cGMP compliant controlled batches of PvSPZ including a wide variety of primary and clonal Pv lines isolated from humans This innovation by Sanaria will offer a consistent quality controlled stock of cryopreserved PvSPZ to promote well controlled reproducible in vitro and in vivo studies in Pv including CHMI This enabling technology will support the development and testing of anti Pv drugs and vaccines in CHMIs world wide just as PfSPZ Challenge has done for Pf CHMIs It will also form the basis of a powerful vaccine approach to preventing Pv malaria when administered with anti malarial chemoprophylaxis the PvSPZ chemoprophylaxis vaccine PvSPZ CVac PUBLIC HEALTH RELEVANCE We propose development of the capacity to manufacture aseptic purified vialed cryopreserved Plasmodium vivax sporozoites PvSPZ that meet regulatory standards and can be used initially to infect human subjects in controlled human malaria infections CHMI to assess the efficacy of anti Pv drugs and vaccines and subsequently as a PvSPZ based vaccine This product will be called Sanaria r PvSPZ Challenge and similar to PfSPZ Challenge will provide the larger malaria community with a tool to assess drugs and vaccines against vivax malaria with a safer quality controlled reagent that exhibits minimal lot to lot variability in potency and is logistically more feasible to administer barring any geographical limitations compared to traditional CHMI using mosquito bites