A Thermostable Measles Vaccine

描述(申请人提供)：麻疹仍然是全球最严重的公共卫生疾病，每年约有50万人或更多人死亡，数百万以上的病例。根除麻疹的主要障碍被认为是缺乏耐热(耐热)疫苗。在这项修订的申请中，我们建议开发一种耐热麻疹疫苗。我们的团队已经开发、测试和实施了一种耐热牛瘟疫苗。麻疹与牛瘟密切相关，因此我们认为我们应该能够使牛瘟模型适用于麻疹。团队成员包括印度血清研究所，该研究所生产的麻疹疫苗比世界上任何人都多(每年生产4亿剂)。顾问包括疾控中心的麻疹实验室，该实验室被公认为世界上最重要的麻疹基因组实验室之一。在这次重新应用中，我们将重点放在使用可接受的辅料开发麻疹疫苗本身上。在与世卫组织和其他机构的磋商中，我们了解到，如果我们的方法成功，它将被视为现有产品的重新配方，因为我们使用的是公认的辅料。这很可能意味着不需要进行人体测试，特别是如果我们能证明我们的产品与目前获得批准并广泛分布的印度血清研究所的产品在基因上相同的话。这一应用方面的改进包括：(1)与印度血清研究所进行更明确的合作，疫苗生产总监、研究员Rajeev Dhere博士参与；(2)更明确地以假设为导向的实验部分；以及(3)在赋形剂和冷冻干燥过程中增加了更新颖的方法。我们增加了大量的实验细节，额外的初步数据，并确定了开发疫苗的新方法。该项目的公共卫生相关性是什么？麻疹每年导致50万人死亡，其中大部分是儿童。疫苗运动未能消除麻疹，因为疫苗在受热时会变质。我们的项目是制造一种新的疫苗，如果没有冷藏，它就不会失去保护人类的能力。

DESCRIPTION (provided by applicant): Measles remains a top-rank public health disease globally, with ~500,000 or more deaths annually and many more millions of cases. The major impediment to measles eradication is believed to be the lack of an heat- stable (thermostable) vaccine. In this revised application, we proposed to develop a thermostable measles vaccine. Our team has already developed, tested, and implemented a thermostable rinderpest vaccine. Measles is closely related to rinderpest, and so we believe that we should be able to adapt the rinderpest model to measles. Team members include the Serum Institute of India, which manufactures more measles vaccine than anyone in the world (> 400,000,000 doses annually). Consultants include the Measles Laboratory of the CDC, acknowledged to be one of the premier measles genomic labs in the world. In this re-application, we focus our efforts on the development of the measles vaccine itself using accepted excipients. In consultations with WHO and others, we have learned that if our approach is successful, it will be viewed as a reformulation of an existing product since we use accepted excipients. This very likely mean that no human testing will be required, especially if we can demonstrate that our product is genetically identical to the currently approved, and widely distributed, Serum Institute of India product. Improvements in this application include: (1) a more explicit collaboration with the Serum Institute of India, with Dr. Rajeev Dhere, Director of Vaccine Production, an Investigator; (2) a more explicitly hypothesis- driven experimental section; and (3) the addition of more novel approaches to the excipients, and freeze- drying process. We have added substantial experimental detail, additional preliminary data, and identified new approaches to the development of the vaccine. What is the public health relevance of this project? Measles kills half a million people, mostly children every year. Vaccine campaigns have failed to eliminate measles because the vaccine goes bad when it is heated. Our project is to make a new vaccine that will not lose its ability to protect people if there is no refrigeration.