Low cost production of rabies virus antigens in rice grain

稻谷中狂犬病病毒抗原的低成本生产

基本信息

批准号：
8122711
负责人：
NING HUANG
金额：
$ 22.66万
依托单位：
VENTRIA BIOSCIENCE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-20 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8122711
关键词：
Accounting Address Agriculture Animals Antibodies Antigens Baculovirus Expression System Binding Biochemical Canis familiaris Case Study Centers for Disease Control and Prevention (U.S.)Cereals Cessation of life Characteristics Cholera Toxin Protomer B Code Communicable Diseases Disease Reservoirs Dose Economic Burden Environment Epitopes Feasibility Studies GTP-Binding Proteins Genes Glycoproteins Human Immune response Immunity Immunization Infection Injection of therapeutic agent Intramuscular Investigation Isoelectric Point Licensing Livestock Mephitidae Molecular Weight Mus Mutate N-terminal Oral Oral Administration Phase Plants Plasmids Prevention Prevention program Process Production Public Health Rabies Rabies Vaccines Rabies virus Raccoons Recombinant Proteins Recombinants Reporting Rice Safety Scientist Seeds Small Business Innovation Research Grant Symptoms System Technology Testing Time Transgenic Organisms United States Vaccinated Vaccination Vaccine Antigen Vaccines Vaccinia Vaccinia virus Vaccinium Viral Viral Antigens Virus Wild Animals base cost cost effectiveness disorder prevention feeding immunogenic immunogenicity meetings mouse model mutant novel pet animal prevent programs protein expression rabies virus glycoprotein G research study scale up

项目摘要

DESCRIPTION (provided by applicant): Rabies is the 10th most lethal infectious diseases in the world, causing approximately 60,000 deaths annually. Rabies is invariably fatal once symptoms occur. Prevention is the key in rabies control. In the US, rabies remains a significant wildlife- management and public-health challenge. The Centers for Disease Control and Prevention (CDC) report that over 90% of rabies cases in the United States are caused by wildlife. The economic burden of rabies in the US exceeds $300 million per year. Oral vaccination is the only effective way to control rabies in wildlife. The only licensed vaccinia-based oral rabies vaccine has cost-effectiveness and safety concerns. There is a need for safer and less expensive oral rabies vaccine both domestically and internationally. Here we propose to develop an oral rabies vaccine in rice grain using our proprietary protein expression technology. We think favorable safety profile, low production costs and high level expression of antigen of our expression system will make a safer vaccine at an affordable cost. In the present SBIR feasibility study, Ventria Bioscience and CDC will collaborate to develop four recombinant plasmid constructs of rabies virus glycoprotein genes. Using the constructed genes, we will develop transgenic rice plants to obtain transgenic seeds. After confirmed by viral glycoprotein expression analysis, devitalized transgenic rice grain will be fed in a mouse model to test oral immune responses and its protection in rabies challenge. We expect at least 1 of the 4 transgenic rice lines will generate at least 80% of protection in the mouse model. PUBLIC HEALTH RELEVANCE: Current oral rabies vaccine has limitation of both safety concern and high cost. We propose to produce the vaccine in rice grain which is safe and can be produced economically. The vaccine, upon meeting all production, quality, and regulatory requirements, would be used in baits for state and federal rabies prevention programs.

描述（由申请人提供）：狂犬病是世界上第十大致命的传染病，每年造成约60,000人死亡。一旦发生症状，狂犬病总是致命的。预防是狂犬病控制的关键。在美国，狂犬病仍然是一个重大的野生动植物管理和公共卫生挑战。疾病控制与预防中心（CDC）报告说，美国超过90％的狂犬病病例是由野生动植物引起的。美国狂犬病的经济负担每年超过3亿美元。口服疫苗接种是控制野生动植物中狂犬病的唯一有效方法。唯一持牌疫苗的口腔狂犬病疫苗具有成本效益和安全性问题。在国内和国际上都需要更安全，更便宜的口腔狂犬病疫苗。在这里，我们建议使用我们专有的蛋白质表达技术在水稻颗粒中开发口腔狂犬病疫苗。我们认为，有利的安全性概况，低生产成本和表达系统抗原的高水平表达将以可承受的成本制造更安全的疫苗。在目前的SBIR可行性研究中，Ventria Bioscience和CDC将合作开发狂犬病病毒糖蛋白基因的四种重组质粒构建体。使用构造的基因，我们将开发转基因水稻植物以获得转基因种子。在通过病毒糖蛋白表达分析确认后，将在小鼠模型中喂食均活化的转基因水稻颗粒，以测试口服免疫反应及其在狂犬病挑战中的保护。我们预计，在4种转基因稻管中，至少有1条将在小鼠模型中产生至少80％的保护。公共卫生相关性：当前的口腔狂犬病疫苗限制了安全问题和高成本。我们建议在水稻谷物中生产疫苗，该疫苗是安全的，可以在经济上生产。满足所有生产，质量和监管要求后，该疫苗将用于州和联邦狂犬病预防计划的诱饵。