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

描述(申请人提供)：狂犬病是一种致命的疾病，估计每年导致4-7万人死亡。它最常通过被感染的野生或野生动物(如蝙蝠、浣熊、臭鼬、狐狸、雪貂、猫或狗)的叮咬和唾液传播。作为诱饵的口服疫苗在咀嚼食物的动物身上取得了成功，从而使疫苗诱饵与口腔和喉咙粘膜接触，引发免疫反应。然而，犬类(狗、狐狸、郊狼)是人类感染这种疾病的主要媒介，它们不会咀嚼它们的食物或诱饵；相反，它们会狼吞虎咽，导致疫苗在胃酸中被摧毁。 在我们的第一阶段项目中，我们结合了两种技术来制备一种新型狂犬病疫苗，设计成在环境温度和恶劣环境下保持稳定，例如在到达小肠的途中通过胃酸和胆汁分泌，在那里我们建议它可以通过肠道粘膜对动物进行免疫。PI正在申请专利的“蒸发保存”(PBV)技术将敏感的生物物质固定在“玻璃状态”下，使它们在常温下保持稳定，该技术已与藻酸盐凝胶封装一起用于保护疫苗免受热和化学损害。科大利用PBV干燥保存了两种藻酸盐包裹的疫苗VRG(基于牛痘)和ERA(基于狂犬病)。我们超过了疫苗在60℃平衡1小时和37℃平衡2周后的最初目标规格。 二期工程的具体目标是：1)优化海藻酸凝胶微球干燥保存狂犬病疫苗的配方。2)研制狂犬病疫苗动物诱饵核(RVABN)。3)在动物研究中评估疫苗产品的效力--特别是狐狸和狗--对抗狂犬病挑战。 该项目的长期目标是生产一种在野外稳定的以诱饵形式分泌的狂犬病口服疫苗。这种疫苗一旦被野生动物食用，不会在胃肠道内被破坏，并会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有限公司合作，后者将提供疫苗并帮助进行动物研究。 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 a deadly disease, estimated to cause 40-70 thousand deaths per year. It is most often spread by a bite and saliva from an infected wild or feral animal (e.g., bats, raccoons, skunks, foxes, ferrets, cats, or dogs). Oral vaccines in bait have been successful with animals that chew their food, thus allowing the vaccine bait to come into contact with the mouth and throat mucosa to elicit the immune response. However, canid species (dogs, foxes, coyotes) ,the primary vectors of the disease to humans, do not chew their food or the bait; rather it gulped down causing the vaccine to be destroyed in the stomach acid. For our Phase 1 project, we combined two technologies to prepare a novel form of rabies vaccine, designed to be stable at ambient temperatures and in harsh environments, such as during the journey through stomach acid and bile secretion on its way to the small intestine where we propose it can immunize the animal through the intestinal mucosa. The PI's patent pending "Preservation by Vaporization" (PBV) technology which immobilizes sensitive biologicals in the "glass state" so they are stable at ambient temperatures has been utilized with alginate gel encapsulation to protect vaccines from heat and chemical damage. UST utilized PBV to dry-preserve two alginate-encapsulated vaccines VRG (vaccinia-based) and ERA (Rabies based). We exceeded our original target specifications for vaccine stability during 1 hour equilibration at 60¿C, and after 2 weeks at 37¿C. The specific aims of the Phase II project are to: 1) Optimize formulation of dry preserved rabies vaccines encapsulated in alginate gel microspheres. 2) Formulate Rabies Vaccine Animal Bait Nucleus (RVABN) filled with VRG and with ERA vaccines. 3) Evaluate efficacy of the vaccine products in animal studies - specifically foxes and dogs - against a rabies challenge. The long-range goal of this project is to produce an oral vaccine for rabies secreted in bait that is stable in the wild. This vaccine, once eaten by wild animals will not be destroyed in the GI tract and will produce a strong immune response in the intestine. UST will partner with CDC and Merial Ltd. who will provide the vaccine and help to perform animal studies. 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.