Entity

Time filter

Source Type

ROCKVILLE, MD, United States

Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 300.00K | Year: 2016

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


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2016

DESCRIPTION provided by applicant The world needs a highly effective malaria vaccine Sanaria r PfSPZ Vaccine composed of aseptic purified cryopreserved radiation attenuated PfSPZ protected of volunteers in an NIH clinical trial The vaccine has been administered by direct venous inoculation DVI to subjects in Mali Tanzania Equatorial Guinea EG and USA Safety tolerability high grade protection heterologous protection after Controlled Human Malaria Infection durable protection in the field efficacy with doses and safety at x the protective dose have been established Sanaria has met with the World Health Organization to plan for pre qualification and establishment of a Technical Advisory Group for PfSPZ Vaccine administered by DVI In the vaccine will be assessed by DVI in Tanzania Kenya infants Mali Burkina Faso EG Germany and USA The first licensure submission in USA is planned for late Reduction in the number of PfSPZ regimen number of doses and or time to complete an immunization regimen and prolongation of efficacy will reduce costs and improve implementation Being able to immunize by cutaneous or intramuscular routes will increase capacity to immunize young infants and facilitate immunization by less experienced personnel To these ends we have studied adjuvants that augment prolong immune responses Traditional and experimental adjuvants including multiple toll like receptor ligands do not work likely because the vaccine is composed of live attenuated organisms and no licensed adjuvants are known to enhance the CD T cell mediated immunity which appears to underlie protective efficacy against PfSPZ Vaccine A novel glycolipid DW which binds CD d and stimulates iNKT cells has strong adjuvant effects in mice immunized with irradiated P yoelii sporozoites irrPySPZ and enabled reduction to one dose when irrPySPZ were administered by DVI protection and from to doses when administered intradermally protection Protection lasted for at least weeks Four DVI doses during a week of x purified cryopreserved irrPySPZ with and without DW protected and of mice respectively p raising the possibility of an accelerated immunization regimen that would be ideal for travelers and mass administration campaigns In non human primates NHPs DW with PfSPZ Vaccine was well tolerated greatly enhancing the magnitude of splenic CD and CD T cell responses months post vaccination These findings support development of DW for use with PfSPZ Vaccine administered both by intravascular and traditional routes to allow for reduced cost of goods rapid immunization and increased durability of protection In this project we will assess DW with rodent human and simian SPZ in mice and NHPs and manufacture DW in compliance with cGMPs Accomplishing the Specific Aims of this proposal will provide the foundation for the first phase clinical trial of PfSPZ Vaccine administered with DW and eventual use of this combination for rapid and cost effective immunization of travelers military and for mass malaria elimination campaigns PUBLIC HEALTH RELEVANCE In our screens to identify an adjuvant that can promote dose sparing and prolong duration of protection with an attenuated malaria vaccine a novel glycolipid DW that binds CD d and stimulates iNKT cells was the only agent over several TLR ligands tested to demonstrate significant enhancement in a mouse malaria model We propose further pre clinical characterization of adjuvant activity in mice and primates to support its inclusion with Sanariaandapos s radiation attenuated PfSPZ Vaccine in order to significantly enhance vaccine potency efficacy and feasibility of use


Patent
Sanaria, Inc. | Date: 2012-12-28

Disclosed are substantially purified


Patent
Sanaria, Inc. | Date: 2011-04-25

This application relates to preventing malaria by administering a vaccine. More particularly, this invention relates to a vaccine against malaria infection compromising the administration of attenuated sporozoites to a human or animal.


Patent
Sanaria, Inc. | Date: 2010-08-27

Disclosed are substantially purified

Discover hidden collaborations