Automated Salivary Gland Dissection for Manufacture of Malaria PfSPZ Vaccine

自动唾液腺解剖用于制造疟疾 PfSPZ 疫苗

基本信息

批准号：
8098964
负责人：
STEPHEN Lev HOFFMAN
金额：
$ 29.96万
依托单位：
SANARIA, INC.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8098964
关键词：
Address Africa Applied Research Area Attenuated Automation Blood capillaries Cessation of life Chest Child Clinical Clinical Trials Collaborations Collection Computer Vision Systems Culicidae Cyclic GMP Development Dissection Engineering Female Adolescents Gland Goals Grant Human Individual Infant Intervention Investigational New Drug Application Lead Malaria Malaria Vaccines Manuals Marketing Mechanics Methods Microscope Military Personnel Pattern Phase Phase I Clinical Trials Physical Chemistry Plasmodium falciparum Positioning Attribute Procedures Process Qualifying Robotics Safety Salivary Glands Schools Small Business Innovation Research Grant Sporozoites Staging Suction System Techniques Technology Time Training Translating Universities Vaccines Vision arm capillary cost immunogenicity innovative technologies instrumentation manufacturing process manufacturing scale-up meetings novel operation protective efficacy public health relevance scale up success tool

项目摘要

DESCRIPTION (provided by applicant): Sanaria was founded in 2003 to develop and commercialize an attenuated sporozoite Plasmodium falciparum (Pf) (PfSPZ) vaccine against malaria. Since then Sanaria has established a manufacturing process, manufactured the PfSPZ Vaccine under cGMPs, submitted an investigational new drug application (IND) to the FDA, received clearance from the FDA to proceed to clinical trials, and initiated the first Phase 1 clinical trial to assess safety, immunogenicity, and protective efficacy of SANARIA PfSPZ Vaccine in May 2009. The PfSPZ vaccine is comprised of Pf sporozoites extracted from infected mosquitoes and a short term challenge for Sanaria involves the optimization of this extraction step in its manufacturing process. Currently, human operators manually carry out the critical task of isolating the sporozoites by serially dissecting salivary glands from individual mosquitoes. Sanaria has established this procedure as a reliable, reproducible, consistent, and efficient process. In the next phase of development, as we optimize the efficiency and expand the scale of vaccine manufacturing, automation of mosquito dissection will prove to be beneficial on several fronts. It will enable us to cut the costs of supporting a large taskforce of skilled technicians, the time taken to train and qualify them and the dedicated space necessary for a scaled-up manual operation. Therefore in this SBIR proposal, we focus on successfully developing strategies to mechanize the process of dissection and collection of mosquito salivary glands. In collaboration with the School of Engineering and Applied Sciences at Harvard University we propose to develop novel instrumentation and innovative technologies to meet this goal. These will be addressed in three specific aims in which we will develop procedures that will allow batch processing of mosquitoes to isolate intact salivary glands with minimal manual involvement. This will be achieved using mechanical engineering and physical chemistry principles. First, in specific aim 1 we will create ordered arrays of mosquitoes and in specific aim 2 we will develop methods to decapitate mosquitoes and to extract and collect the salivary glands without losing sporozoites. The technology described here is expected to achieve very high throughput and process scalability. In specific aim 3 we propose a direct substitution of our current dissection configuration with robotic arms and vision guided microscope systems. This serial processing approach will circumvent the need to create mosquito assemblies and involves limited, if any, manual operation. The end-product from the advanced automated techniques however must match or exceed Sanaria's current standards for vaccine yield and potency and will drive the decision to translate our current method of mosquito salivary gland dissection to an automated platform. PUBLIC HEALTH RELEVANCE: Malaria causes >300 million clinical cases and 1 million deaths annually, is responsible for >1% loss of GDP in Africa annually and is a serious concern for travelers and military personnel. Sanaria's goal is to develop and commercialize a >90% protective malaria vaccine for three primary markets with a potential for >$1 billion annual revenues: 1) Travelers from the developed world to malaria endemic areas. 2) Infants and young children in the developing world. 3) Adolescent girls in the developing world. Success in this Phase I SBIR will lead to a significant increase in the efficiency of manufacture of the PfSPZ Vaccine that will facilitate scale-up of manufacturing and significantly reduce the cost of goods.

描述（由申请人提供）：Sanaria成立于2003年，旨在开发和商业化衰减的孢子虫恶性疟原虫（PF）（PFSPZ）（PFSPZ）疫苗针对疟疾。从那以后，Sanaria建立了制造过程，根据CGMPS制造了PFSPZ疫苗，向FDA提交了研究新药应用（IND），从FDA获得了从FDA进行的许可，以进行临床试验，并启动了第一阶段1临床试验，以评估Sanaria PFSPSPSSSS的安全性，MAYSSSSSSSS SANARIA ISSSS SANARIA ISSSS SANARIA ISSSS SANARIA ISSSS SANARIA ISSSS SANARIA FACRINE和2009年。从感染的蚊子中提取的PF子孢子和Sanaria的短期挑战涉及在其制造过程中优化此提取步骤。目前，人工操作员通过从单个蚊子中串行剖析唾液腺来手动执行孤立的孢子虫的关键任务。 Sanaria已将此程序确立为可靠，可重复，一致和有效的过程。在下一阶段开发中，随着我们优化效率并扩大疫苗制造的规模，蚊子解剖的自动化将被证明在几个方面是有益的。这将使我们能够削减支持大量熟练技术人员的工作成本，训练和限定他们的时间以及扩展手动操作所需的专用空间所花费的时间。因此，在该SBIR提案中，我们着重于成功制定策略来机械化蚊子唾液腺的解剖和收集过程。在哈佛大学的工程和应用科学学院合作，我们建议开发新颖的仪器和创新技术以实现这一目标。这些将以三个特定的目的来解决，我们将开发程序，以允许蚊子的批处理处理以最少的手动参与分离完整的唾液腺。这将是使用机械工程和物理化学原则来实现的。首先，在特定的目标1中，我们将创建有序的蚊子阵列，在特定的目标2中，我们将开发斩首蚊子并提取和收集唾液腺而不会失去孢子虫的方法。预计此处描述的技术将达到很高的吞吐量和过程可扩展性。在特定的目标3中，我们建议用机器人臂和视力引导的显微镜系统直接替换当前的解剖配置。这种串行处理方法将规避需要创建蚊子组件并涉及手动操作（如果有的话）。但是，来自高级自动化技术的最终产品必须匹配或超过Sanaria的当前疫苗收益和效力标准，并将推动将我们当前的蚊子唾液腺解剖方法转化为自动化平台的决定。公共卫生相关性：疟疾每年造成3亿次临床病例和100万人死亡，每年造成1％的GDP损失> 1％，这对旅行者和军事人员来说是一个严重的关注。 Sanaria的目标是开发和商业化> 90％的防护性疟疾疫苗，以供三个主要市场，年收入> 10亿美元，1）来自发达国家到疟疾特有地区的旅行者。 2）发展中国家的婴儿和幼儿。 3）发展中国家的青春期女孩。在这一阶段，SBIR的成功将导致PFSPZ疫苗的制造效率显着提高，这将促进制造规模并大大降低商品成本。