Attenuated Malaria Sporozoite Vaccine

减毒疟疾子孢子疫苗

• 批准号: 6932884
• 负责人: STEPHEN Lev HOFFMAN
• 金额: $ 100万
• 依托单位: SANARIA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6932884
• 关键词: Plasmodium falciparum; attenuated microorganism; biotechnology; controlled environment; cryopreservation; drug design /synthesis /production; handbook; immunocytochemistry; laboratory mouse; laboratory rabbit; malaria; malaria vaccines; method development; spores; vaccine development

DESCRIPTION (provided by applicant): Malaria causes an estimated 500 million clinical cases and up to 2.7 million deaths annually, is responsible for a loss of greater than 1% 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 attenuated Plasmodium falciparum (Pf) sporozoite vaccine for 2 primary markets with a potential for > $1 billion annual revenues; 1) Travelers from the developed world and 2) Infants and young children in the developing world. In limited trials, this type of immunization has protected > 90% of human volunteers against experimental Pf challenge, protect for > 10 months after last immunization, and protect against heterologous parasite challenge. No other experimental malaria vaccine under development has been shown to approach these performance characteristics. Heretofore it has been considered impractical to develop such a vaccine, because it was not considered feasible to, 1) Immunize humans by a clinically acceptable parenteral route, 2) Produce adequate quantities of sporozoites, and 3) Practically produce the aseptic, homogenously purified and characterized, radiation attenuated, stable, cryopreserved sporozoites needed to meet regulatory and commercial standards for a vaccine. Phase I funding for this project supported the successful demonstration in the P. yoelii (Py) rodent model system that it was feasible to produce, characterize and administer by a clinically acceptable route a purified, cryopreserved radiation attenuated malaria sporozoite vaccine. Using Phase I and other funding Sanaria has generated data indicating that all of the potential feasibility questions are not obstacles, and further work is solidifying these findings. The Phase II project is to, 1) Complete process development and generation of a technology transfer package, including standard operating procedures for clinical manufacture and characterization of the vaccine, 2) Manufacture and characterize the first engineering run (lot) of the vaccine, 3) Manufacture the vaccine under cGMP conditions. 4) Conduct all studies required for Investigational New Drug Application (IND) submission to the FDA, and 5) Write and submit the IND. A phase III follow up project will assess the safety, immunogenicity and protective efficacy of the vaccine in experimentally challenged volunteers (Phase I/I la clinical trial) in Maryland and in naturally exposed adults (Phase I/lib) in Ghana. Success in these first clinical trials will lead to a massive development effort leading to licensure and deployment of the vaccine.

描述（由申请人提供）：疟疾估计导致5亿次临床病例，每年270万例死亡，每年导致非洲损失超过GDP的1％，这是旅行者和军事人员的严重关注。 Sanaria的目标是开发和商业化> 90％的保护性衰减恶性疟原虫（PF）Sporozoite疫苗，用于2个主要市场，年收入> 10亿美元； 1）来自发达国家的旅行者和2）发展中国家的婴儿和幼儿。在有限的试验中，这种免疫能够保护人类志愿者的90％> 90％的实验性PF挑战，在上次免疫后预防> 10个月，并防止异源寄生虫挑战。未发育中的其他实验性疟疾疫苗可用于这些性能特征。 Heretofore it has been considered impractical to develop such a vaccine, because it was not considered feasible to, 1) Immunize humans by a clinically acceptable parenteral route, 2) Produce adequate quantities of sporozoites, and 3) Practically produce the aseptic, homogenously purified and characterized, radiation attenuated, stable, cryopreserved sporozoites needed to meet regulatory and commercial standards for a vaccine.该项目的第一阶段资金支持P. yoelii（Py）啮齿动物模型系统的成功演示，可以通过临床上可接受的途径产生，表征和给药。使用I期和其他资金SANARIA产生了数据，表明所有潜在的可行性问题都不是障碍，并且进一步的工作正在巩固这些发现。第二阶段项目是：1）完整的过程开发和生成技术转移包，包括疫苗的临床制造和表征的标准操作程序，2）制造和表征疫苗的第一次工程运行（LOT），3）在CGMP条件下生产疫苗。 4）进行调查新药应用所需的所有研究（IND）提交给FDA，5）写并提交IND。第三阶段的随访项目将评估疫苗在马里兰州的实验挑战志愿者（I/I阶段临床试验）和加纳自然暴露的成年人（I/LIB）中的安全性，免疫原性和保护性。在这些第一次临床试验中的成功将导致大规模的发展努力，从而导致疫苗的许可和部署。