A Unique Automated Bioreactor for Rearing Aseptic Mosquitoes from Larvae to Adults to Support Manufacture of Sanaria PfSPZ Products.

独特的自动化生物反应器，用于培育从幼虫到成虫的无菌蚊子，以支持 Sanaria PfSPZ 产品的生产。

• 批准号: 9620426
• 负责人: Peter F. Billingsley
• 金额: $ 30万
• 依托单位: SANARIA, INC.
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-18 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9620426
• 关键词: Adult; Africa; African; Air; Anopheles Genus; Attenuated; Automation; Biological; Biological Assay; Bioreactors; Cessation of life; Characteristics; Chemoprophylaxis; Child; Clinical; Clinical Trials; Country; Culicidae; Custom; Cyclic GMP; Disease; Dissection; Ebola virus; Ensure; Environment; Epidemic; European; Excision; Falciparum Malaria; Geographic Locations; Germany; Grant; Growth; Hand; Harvest; Heating; Hour; Human; Human Resources; Immunity; Incubators; Individual; Infection; Infection prevention; Institutes; Larva; Licensing; Licensure; Malaria; Malaria Vaccines; Mali; Manuals; Mass Vaccinations; Medical; Methods; Nutrient; Output; Parasites; Phase; Phase III Clinical Trials; Plasmodium falciparum; Plasmodium falciparum vaccine; Prevention; Price; Process; Production; Pupa; Radiation; Reporting; Reproducibility; Risk; Safety; Salivary Glands; Sea; Shapes; Site; Small Business Innovation Research Grant; Sporozoite vaccine; Sporozoites; Stream; System; Tanzania; Testing; Tube; Vaccines; Waste Products; base; commercialization; cost; design; egg; fitness; flasks; human old age (65+); improved; malaria infection; manufacturing process; protective efficacy; scale up; seal; success; tool; transmission process

Project Summary/Abstract: The annual estimated burden of malaria has increased to 216M clinical episodes and 445,000 deaths, and annual losses of >$12B of GDP to malaria in Africa alone. The world needs a malaria vaccine. Sanaria’s Plasmodium falciparum sporozoite (PfSPZ) vaccines have protected 100% of subjects against controlled human malaria infection (CHMI) in five clinical trials in the U.S., Germany, Tanzania, and Mali; protected adults at least for 6 months against intense, heterogeneous transmission of Pf in two clinical trials in Mali, and are now being assessed in clinical trials in 5 months to 65-year old’s in 5 African countries and in adults in 2 European countries as well as 3 sites in the US. The plan is to initiate the first Phase 3 clinical trials to support submission of a Biologics License Application to the FDA in the US in the second half of 2018, and in Africa in the first half of 2019. Sanaria’s PfSPZ-based vaccines contain aseptic, purified, cryopreserved, live Plasmodium falciparum (Pf) sporozoites (SPZ) that are manufactured in aseptically reared Anopheles stephensi mosquitoes. The current method of aseptic mosquito production, while robust and reproducible, relies heavily upon manpower and large quantities of expensive consumables, and requires significant space. Semi-automation of mosquito dissection to remove salivary glands developed under another SBIR grant is expected to increase the efficiency of the process to 750-1,000 mosquitoes per hour per operator in the first half of 2018. Thus, production of mosquitoes is now the bottleneck and most expensive step in the GMP manufacture of PfSPZ vaccines. The overarching aim of this project is therefore to develop methods to reduce manpower and consumable costs and overall space requirements by developing a semi- automated system for culturing (manufacturing) aseptic mosquitoes. In specific aim 1, we will design, build and test a bioreactor for hands-free, aseptic culturing from eggs to larvae to adult mosquitoes. This bioreactor will be developed to 1) meet all GMP requirements, 2) remove the need for expensive consumables to increase output, 3) reduce human costs, 4) eliminate the need for many of the biological safety cabinets used in mosquito production, and 5) be adaptable for eventual removal of incubators from mosquito production. We will demonstrate that the new bioreactor is capable of maintaining the critical aseptic environment for the larval cultures, and that the mosquitoes raised in the larval bioreactor show equivalence with those produced by current methods. In specific aim 2 we will develop apparatus for automated harvesting of adult mosquitoes. Our aim is to be able to transfer newly emerged adult mosquitoes directly and hands free from the larval bioreactors into big aseptic mosquito containers in which the mosquitoes will be fed upon gametocytes and maintained until the day of extraction of PfSPZ from mosquitoes. Developing the larval bioreactor will lead to a sea change in Sanaria’s capacity to manufacture its PfSPZ products, putting Sanaria on track for mass-scale manufacturing at phase 3 GMP compliance at a significantly reduced cost.

项目摘要/摘要：疟疾的年估计负担已增加到2.16亿临床发作