Automating mosquito microdissection for a malaria PfSPZ vaccine

自动显微解剖蚊子以生产疟疾 PfSPZ 疫苗

• 批准号: 10258416
• 负责人: Sumana Chakravarty
• 金额: $ 100万
• 依托单位: SANARIA, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-20 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258416
• 关键词: Africa South of the Sahara; Authorization documentation; Automation; Body part; COVID-19; COVID-19 pandemic; Cessation of life; Characteristics; Chest; Child; Clinical Trials; Collection; Comb animal structure; Computer Vision Systems; Culicidae; Cyclic GMP; Decapitation; Development; Devices; Dissection; Ensure; Environment; Equipment; Falciparum Malaria; Fatigue; Feasibility Studies; Geometry; Gland; Goals; Head; Hour; Human; Human Resources; Individual; Injections; Insecta; Investments; Lead; Licensure; Malaria; Malaria Vaccines; Manuals; Marketing; Measures; Methodology; Methods; Microdissection; Microscope; Modeling; Modification; Molds; Needles; Outcome; Output; Phase; Phase III Clinical Trials; Plasmodium falciparum; Plasmodium falciparum vaccine; Population; Procedures; Process; Production; Research Personnel; Robotics; Running; Safety; Salivary Glands; Scheme; Sporozoites; Stainless Steel; System; Technology; Testing; Time; Training; Vaccines; Vision; base; cGMP production; commercialization; cost; cost effective; design; experience; feeding; fight against; human error; improved; in vivo; innovation; insight; machine learning algorithm; manufacturing scale-up; multidisciplinary; operation; process optimization; protective efficacy; prototype; robotic system; software systems; success; tool

ABSTRACT Despite annual investments of >$3 billion for intensive control measures, in 2018, the 228 million cases of malaria were an increase of ~16 million cases over 2015, and no decrease in number of deaths. The impact of available malaria control measure has plateaued. Moreover, WHO estimates deaths from malaria could double across sub-Saharan Africa this year due to disruptions in access to control measures due to the current global COVID-19 pandemic malaria. New tools, especially a vaccine, are needed. Only broad deployment of an effective vaccine holds the promise of true elimination or eradication, especially in the face of sudden developments like COVID-19. More than 98% of all deaths from malaria are caused by Plasmodium falciparum (Pf). Thus, a vaccine against Pf malaria is the priority. Sanaria is moving in 2021 to Phase 3 clinical trials of its Pf sporozoite (SPZ), PfSPZ Vaccine, and is planning for marketing authorization (licensure) from FDA and EMA in 2022/2023. Over the next 5-10 years we aim to decrease the cost of goods (COGs) and efficiency of production of PfSPZ vaccines so they can be used most effectively and economically by individuals who suffer the most from malaria. Microdissection of mosquitoes is a crucial step in extraction of PfSPZ vaccine products, and ensures a 10,000-fold purification away from irrelevant mosquito parts as the starting material for downstream purification procedures that then achieve a final product purity of 99.9%. To-date, mosquito salivary gland PfSPZ have demonstrated in vivo infectivity/potency superior to those extracted from whole mosquitoes, or grown outside a mosquito. However, extraction of mosquito salivary glands is a rate-limiting, labor-intensive, expensive step in production of PfSPZ-based vaccines. The overarching aim of this proposal is to enable implementation of an interim semi-automated dissection device in cGMP production of PfSPZ-based vaccines against malaria, and develop an integrated dissection system incorporating multiple automation steps downstream of mosquito orientation, for commercial-scale manufacturing. The unique application of robotic technology, state-of-the art computer vision and machine learning algorithms, and software systems to production-scale processing of very small insects in cleanrooms not only advances manufacturing capabilities, but also represents a spectrum of milestone innovations in automation. Success in this project involving a highly-skilled multi-disciplinary team of investigators, manufacturing and quality experts will decidedly lead to further streamlining and process optimization during the key step of isolating mosquito salivary glands for manufacture of our highly effective PfSPZ-based vaccines. The breakthroughs that initially defined a vaccine that is far superior to competing technologies in both safety and protective efficacy, will continue, as we advance in the proposed studies to make vaccine extraction more cost-effective due to greater efficiencies, mitigation of human error and operator fatigue, reduced timeframes, greatly reduced training periods, and increased product purity, towards deployment of a highly-impactful tool in the fight against malaria.

摘要 尽管每年投入30亿美元用于强化控制措施，但2018年，2.28亿起 与2015年相比，疟疾病例增加了约1600万例，死亡人数没有减少。网络的影响 现有的疟疾控制措施已经停滞不前。此外，世卫组织估计死于疟疾的人数可能会翻一番 今年在撒哈拉以南非洲，由于当前全球气候变化，控制措施的获取中断 新冠肺炎大流行疟疾。需要新的工具，特别是疫苗。只有广泛部署 有效的疫苗有望真正消除或根除，特别是在面对突然的 像新冠肺炎这样的发展。所有疟疾死亡的98%以上是由恶性疟原虫引起的 (Pf)。因此，针对PF疟疾的疫苗是当务之急。Sanaria将于2021年进入其第三阶段临床试验 PfSPZ子孢子(SPZ)，PfSPZ疫苗，并计划从FDA和 2022/2023年的EMA。在接下来的5-10年里，我们的目标是降低商品成本(齿轮)和效率 生产PfSPZ疫苗，以便受难者能够最有效、最经济地使用这些疫苗 其中最多的是疟疾。对蚊子进行显微解剖是提取PfSPZ疫苗产品的关键一步， 并确保从不相关的蚊子部位提纯一万倍，作为 下游提纯程序，然后获得99.9%的最终产品纯度。到目前为止，蚊子 唾液腺PfSPZ在体内的感染性/效力优于从全唾液中提取的 蚊子，或在蚊子外面生长。然而，蚊子唾液腺的提取是一个速度限制， 生产以PfSPZ为基础的疫苗的劳动密集型、昂贵的一步。这项建议的主要目的是 在以PfSPZ为基础的cGMP生产中实现临时半自动解剖设备 针对疟疾的疫苗，并开发包含多个自动化步骤的集成解剖系统 在蚊子定向的下游，用于商业规模的生产。机器人的独特应用 技术、最先进的计算机视觉和机器学习算法以及软件系统 在洁净室中对非常小的昆虫进行大规模的生产加工不仅提高了制造能力， 但也代表了自动化领域的一系列里程碑式的创新。此项目的成功涉及 由调查人员、制造和质量专家组成的高技能多学科团队将决定性地导致 在分离蚊子唾液腺的关键步骤中进一步精简和优化流程 生产我们基于PfSPZ的高效疫苗。最初定义疫苗的突破 这种在安全性和保护有效性方面远远优于竞争对手的技术将继续下去，因为我们 由于效率更高而使疫苗提取更具成本效益的拟议研究进展， 减少人为错误和操作员疲劳，缩短时间框架，大大缩短培训周期，以及 提高产品纯度，以部署一种在防治疟疾方面具有高度影响力的工具。