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

• 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
• 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

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传染病，每年造成约 60,000 人死亡。一旦出现症状，狂犬病总是致命的。预防是控制狂犬病的关键。在美国，狂犬病仍然是野生动物管理和公共卫生面临的重大挑战。美国疾病控制与预防中心 (CDC) 报告称，美国 90% 以上的狂犬病病例是由野生动物引起的。美国每年因狂犬病造成的经济负担超过 3 亿美元。口服疫苗是控制野生动物狂犬病的唯一有效方法。唯一获得许可的基于牛痘的口服狂犬病疫苗存在成本效益和安全性问题。国内外都需要更安全、更便宜的口服狂犬病疫苗。在这里，我们建议使用我们专有的蛋白质表达技术在米粒中开发口服狂犬病疫苗。我们认为，良好的安全性、较低的生产成本和我们的表达系统抗原的高水平表达将以可承受的成本生产出更安全的疫苗。在目前的 SBIR 可行性研究中，Ventria Bioscience 和 CDC 将合作开发四种狂犬病病毒糖蛋白基因的重组质粒构建体。利用构建的基因，我们将培育转基因水稻植株，获得转基因种子。经过病毒糖蛋白表达分析证实后，失活的转基因米粒将被喂养到小鼠模型中，以测试口腔免疫反应及其在狂犬病攻击中的保护作用。我们预计 4 个转基因水稻品系中的至少 1 个将在小鼠模型中产生至少 80% 的保护。 公共卫生相关性：目前的口服狂犬病疫苗存在安全问题和高成本的局限性。我们建议用大米生产疫苗，既安全又经济。该疫苗在满足所有生产、质量和监管要求后，将用于州和联邦狂犬病预防计划的诱饵中。