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: 10613471
• 负责人: Sumana Chakravarty
• 金额: $ 95.79万
• 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 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10613471
• 关键词: Acceleration; Africa South of the Sahara; Authorization documentation; Automation; Body part; COVID-19; COVID-19 pandemic; Cessation of life; Characteristics; Chest; Child; Clinical Trials; Collection; Computer Vision Systems; Culicidae; Cyclic GMP; Decapitation; Dedications; 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; Modification; Molds; Needles; Outcome; Output; Phase; Phase III Clinical Trials; Plasmodium falciparum; Plasmodium falciparum vaccine; Population; Procedures; Process; Production; Research Personnel; Robotics; Safety; Salivary Glands; Scheme; Sporozoites; Stainless Steel; System; Systems Integration; Technology; Testing; Time; Training; Vaccines; Vision; aspirate; authority; cGMP production; commercialization; cost; cost effective; design; ergonomics; experience; feeding; fighting; human error; improved; in vivo; innovation; insight; machine learning algorithm; manufacture; manufacturing capabilities; manufacturing run; manufacturing scale-up; multidisciplinary; operation; process optimization; protective efficacy; prototype; robotic system; skills; 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.

抽象的 尽管针对密集控制措施的年度投资约为30亿美元，但2018年，2.28亿案件 疟疾比2015年增加了约1600万例，死亡人数没有减少。的影响 可用的疟疾控制措施已经平稳。此外，谁估计疟疾死亡可能两倍 由于当前全球的访问权限，整个撒哈拉以南非洲地区的访问中断 Covid-19-19个大流行疟疾。需要新工具，尤其是疫苗。仅广泛部署 有效的疫苗有真正消除或根除的承诺，尤其是在突然的情况下 诸如Covid-19之类的发展。疟疾所有死亡人数中有98％是由恶性疟原虫引起的 （PF）。因此，针对PF疟疾的疫苗是优先事项。萨纳里亚（Sanaria PF Sporozoite（SPZ），PFSPZ疫苗，并计划从FDA和FDA和 EMA在2022/2023。在接下来的5 - 10年中，我们旨在降低商品成本（COG）和效率 生产PFSPZ疫苗，因此可以最有效，经济地使用它们 来自疟疾的最多。蚊子的显微解剖是提取PFSPZ疫苗产品的关键步骤， 并确保距离无关蚊子的净化10,000倍，作为起始材料 然后达到99.9％的最终产品纯度的下游纯化程序。迄今为止，蚊子 唾液腺PFSPZ已在体内感染性/效力中优于从整体中提取的感染性/效力 蚊子或在蚊子外生长。但是，提取蚊子唾液腺是限制速率的， 基于PFSPZ的疫苗生产劳动密集型，昂贵的步骤。该提议的总体目的是 为了实现基于PFSPZ的CGMP生产中的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综合解剖系统 蚊子定向的下游，用于商业规模的制造。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 洁净室中非常小的昆虫的生产规模加工不仅可以提高制造能力，还可以 但这也代表了自动化中的里程碑创新。这个项目的成功涉及 高技能的调查人员，制造业和质量专家的多学科团队将绝对导致 在隔离蚊子唾液腺的关键步骤中进一步简化和过程优化 生产我们高效的基于PFSPZ的疫苗。最初定义疫苗的突破 这比我们的安全和保护功效方面的竞争技术要好得多，随着我们 在拟议的研究中，由于效率较高，提取疫苗提取更具成本效益 缓解人为错误和操作员疲劳，减少时间表，大大减少培训期以及 提高产品纯度，以在与疟疾作斗争中部署高度影响的工具。

项目成果

A Mosquito Pick-and-Place System for PfSPZ-based Malaria Vaccine Production.

• DOI: 10.1109/tase.2020.2992131
• 发表时间: 2021-01
• 期刊: IEEE transactions on automation science and engineering : a publication of the IEEE Robotics and Automation Society
• 作者: Phalen H;Vagdargi P;Schrum ML;Chakravarty S;Canezin A;Pozin M;Coemert S;Iordachita I;Hoffman SL;Chirikjian GS;Taylor RH
• 通讯作者: Taylor RH