Formulation of Ambient Temperature and Humidity Stable Rabies Vaccines for Oral D

描述(申请人提供)：狂犬病是一种急性和致命的疾病，由中枢神经系统的病毒感染引起，通常通过被感染的(狂犬病)动物(例如蝙蝠、浣熊、臭鼬、狐狸、雪貂、猫或狗)的叮咬和唾液传播。每年死于狂犬病的人数估计在4万到7万之间。就像许多人畜共患病一样，保护人类的唯一方法就是消灭动物宿主中的疾病。对于自养的狗和其他宠物，非肠道接种狂犬病疫苗是可行的，而对于野生和流浪动物，则需要口服疫苗，并在食物或诱饵中提供狂犬病疫苗。目前，约有15个州为野生动物分发可食用狂犬病疫苗，试图根除这种疾病。这些疫苗的问题是它们在环境条件下不稳定，很容易在动物的胃肠道(GI)系统中被破坏。迫切需要一种新的动物口服狂犬病疫苗递送系统。疫苗必须免受阳光、高温和潮湿的影响。此外，还必须保护它免受胃液和十二指肠胆汁的损害。该产品应在动物口中迅速溶解，不能被人工和/或空中投放的诱饵破坏。我们建议结合两种技术来制备一种新形式的狂犬病疫苗，它应该具有良好的产量，将具有成本效益，应该在常温下稳定，并更稳定地穿越胃和十二指肠。蒸发保鲜(PBV)是由PI发明的，拥有一项正在申请专利的专利，它将敏感的生物物质固定在“玻璃状态”下，因此它们在常温下是稳定的。海藻酸凝胶胶囊在该行业已经使用了几年，以保护疫苗免受GI系统的损害。我们建议用PBV干燥包裹在海藻酸凝胶微球中的新鲜狂犬病疫苗。具体目标是：1.制定使用PBV技术的动物狂犬病疫苗干燥方案。展示干保存疫苗在37℃和60℃2下的稳定性。)研制藻酸盐凝胶微球(平均直径约100？)由病毒颗粒和保存液组成，病毒从颗粒中淋失或泄漏的损失最小(小于10%)。3.)制定使用PBV技术对包裹在海藻酸微球中的狂犬病疫苗进行干燥的方案。展示干燥保存的疫苗在37℃和60℃下的稳定性。需要在60摄氏度的短期稳定性才能将疫苗包裹在可食用的氢化油或脂肪中，以确保保护免受环境湿度的影响。该项目的长期目标是生产出在野外稳定、可被野生动物食用、不会在胃肠道内被破坏的诱饵，从而在肠道内产生强烈的免疫反应。科大将与疾控中心和梅里亚公司合作，后者将提供疫苗并进行生存分析。公共卫生相关性：狂犬病每年造成的死亡人数估计在40,000至70,000人之间。在美国，狂犬病患者的生活成本很高，而且还在不断增长，每年超过3亿美元。尽管家畜接种狂犬病疫苗已有多年，但这种预防措施直到最近才被开发出来，以控制野生动物中的狂犬病。开发一种将稳定的狂犬病疫苗嵌入食用氢化油中的诱饵，使疫苗免受阳光、温度、湿度和胃液等因素的影响，可以为野生动物接种疫苗，使它们不会感染狂犬病，从而有助于根除狂犬病。

DESCRIPTION (provided by applicant): Rabies is an acute and deadly disease caused by a viral infection of the central nervous system, most often spread by a bite and saliva from an infected (rabid) animal (e.g., bats, raccoons, skunks, foxes, ferrets, cats, or dogs). The number of deaths due to rabies each year is estimated to be between 40,000-70,000. As it is for many zoonotic diseases, the only way to protect humans is to eliminate the disease in the animal reservoir. Parenteral rabies vaccination is feasible for owned dogs and other pets, whereas oral vaccination is required for wild and stray animals, with the delivery of rabies vaccine within a food or bait. Currently, about 15 states distribute edible rabies vaccines for wild animals in an attempt to eradicate the disease. The problem with these vaccines is that they are not stable in environmental conditions and are easily destroyed in the animal's gastrointestinal (GI) system. There is great need for a new oral rabies vaccine delivery system for animals. The vaccine must be protected from sunlight, high ambient temperatures and humidity. In addition, it must be protected from the damaging effect of gastric juice and bile in the duodenum. The product should readily and instantly dissolve in the animal's mouth, not be destroyed by manual and/or aerial bait distribution. We propose to combine two technologies to prepare a novel form of rabies vaccine that should have good yield, will be cost effective and should be stable at ambient temperatures and more stable traversing the stomach and duodenum. Preservation by Vaporization (PBV) was invented by the PI, has a pending patent and immobilizes sensitive biologicals in the "glass state" so they are stable at ambient temperatures. Alginate gel encapsulation has been used for several years in the industry to protect vaccines from damage in the GI system. We propose to use PBV to dry fresh rabies vaccine encapsulated in alginate gel microspheres. The specific aims are: 1.) Formulate a protocol for drying of rabies vaccines for animals using PBV technology. Demonstrate stability of the dry preserved vaccines at 37oC and 60oC 2.) Develop alginate gel micro spheres (with an average diameter of about 100 ?) comprised of the viral particles and the preservation solution with minimum (less than 10%) loss of the virus by leaching or leaking from the particles. 3.) Formulate a protocol for drying of rabies vaccines encapsulated in the alginate microspheres using PBV technology. Demonstrate stability of the dry preserved vaccines at 37oC and 60oC. The short term stability at 60oC is needed to entrap the vaccines in eatable hydrogenated oils or fats to ensure protection from ambient humidity. The long-range goal of this project is to produce bait that is stable in the wild, would be eaten by wild animals and will not be destroyed in the GI tract, so it will produce a strong immune response in the intestine. UST will partner with CDC and Merial Inc. who will provide vaccine and perform viability assays. PUBLIC HEALTH RELEVANCE: The number of deaths that rabies causes each year is estimated to be between 40,000-70,000. The cost of living with rabies in America is high and growing, exceeding $300 million per year. Although rabies vaccinations have been available for domestic animals for many years, only recently have such preventive measures been developed to control rabies in wildlife. Development of baits that would have stable rabies vaccines embedded in edible hydrogenated oils such that the vaccines are protected from the elements, including sunlight, temperature, humidity and gastric juices, could allow vaccination of wild animals so they do not get rabies, and thus could help eradicate the disease.