Low cost production of rabies virus antigens in rice grain

描述(申请人提供)：狂犬病是世界第十大致命传染病，每年造成约60,000人死亡。一旦出现症状，狂犬病总是致命的。预防是狂犬病控制的关键。在美国，狂犬病仍然是野生动物管理和公共卫生的重大挑战。疾病控制和预防中心(CDC)报告称，美国90%以上的狂犬病病例是由野生动物引起的。美国每年狂犬病的经济负担超过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。无论是在国内还是国际上，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大米谷物中开发一种口服狂犬病疫苗。我们认为，我们的表达系统良好的安全性、低生产成本和高水平的抗原表达将以负担得起的成本制造出更安全的疫苗。在目前的SBIR可行性研究中，Ventria Bioscience和CDC将合作开发狂犬病病毒糖蛋白基因的四个重组质粒构建。利用构建的基因，我们将培育转基因水稻植株，以获得转基因种子。在病毒糖蛋白表达分析证实后，将灭活的转基因大米颗粒喂养小鼠模型，以测试口服免疫反应及其在狂犬病攻击中的保护作用。我们预计，在小鼠模型中，4个转基因水稻品系中至少有1个将产生至少80%的保护作用。 公共卫生相关性：目前的口服狂犬病疫苗既有安全性问题，也有成本高的局限性。我们建议在大米粒中生产安全、经济的疫苗。这种疫苗在满足所有生产、质量和监管要求后，将被用于州和联邦狂犬病预防计划的诱饵。

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.