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

环境温度和湿度稳定的口服 D 型狂犬病疫苗的配制

• 批准号: 7538049
• 负责人: Victor Bronshtein
• 金额: $ 12.58万
• 依托单位: UNIVERSAL STABILIZATION TECHNOLOGIES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538049
• 关键词: 6-Phytase; Achievement; Acute; Affect; Africa; Agreement; Alginates; Americas; Animals; Anthrax disease; Asia; Attenuated; Attenuated Vaccines; Avian Influenza; Bacteria; Biological Assay; Biological Preservation; Bite; Caliber; Canis familiaris; Carbohydrates; Centers for Disease Control and Prevention (U.S.); Central Nervous System Viral Diseases; Cessation of life; Chiroptera; Cold Chains; Condition; DNA Vaccines; Data; Developed Countries; Developing Countries; Development; Disease; Dog Bite; Domestic Animals; Dose; Drops; Drug Formulations; Duodenum; Eating; Economic Burden; Elements; Encapsulated; Ensure; Environment; Enzymes; Exposure to; Fatty acid glycerol esters; Felis catus; Ferrets; Food; Foxes; Freeze Drying; Gastric Juice; Gastrointestinal tract structure; Gel; Generations; Glass; Glycoproteins; Goals; High temperature of physical object; Hour; Human; Humidity; Hydrogels; Immune response; Immunization; Industry; Intestinal Mucosa; Intestines; Lead; Legal patent; Life; Light; Liquid substance; Listeria; Listeriosis; Living Costs; Manuals; Measles; Measles Vaccine; Measures; Meat; Mephitidae; Methods; Microspheres; Numbers; Oils; Oral; Oral cavity; Personal Satisfaction; Phase; Plastics; Polymers; Population; Preventive; Probiotics; Protocols documentation; Public Health; RNA Viruses; Rabies; Rabies Vaccines; Rabies virus; Raccoon Dogs; Raccoons; Range; Refrigeration; Reporting; Saliva; Salmonella; Smallpox; Solid; Solutions; Stomach; Sucrose; Sunlight; Suspension substance; Suspensions; System; Technology; Temperature; Transportation; Tropical Disease; Tularemia; Vaccinated; Vaccination; Vaccines; Vaccinia virus; Vegetable Oils; Vegetables; Viral; Viral Vaccines; Virion; Virus; Week; West Nile virus; Wild Animals; Yellow Fever Vaccine; Zoonoses; base; biodefense; commercial application; cost effective; gastrointestinal system; innovation; melting; novel; novel vaccines; oral vaccine; palm oil; particle; pet animal; positional cloning; programs; rabies virus glycoprotein G; reconstitution; size; technological innovation; vaccine delivery; vaporization

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.

描述（由申请人提供）：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，最常见的是通过被感染（狂犬病）动物的咬伤和唾液传播（例如，蝙蝠、浣熊、臭鼬、狐狸、雪貂、猫或狗）。每年死于狂犬病的人数估计在40，000至70，000之间。正如许多人畜共患病一样，保护人类的唯一方法是消除动物宿主中的疾病。非肠道狂犬病疫苗接种对于拥有的狗和其他宠物是可行的，而口服疫苗则需要野生和流浪动物，狂犬病疫苗在食物或诱饵中递送。目前，大约有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。这些疫苗的问题在于它们在环境条件下不稳定，并且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给药系统。疫苗必须避免阳光照射、高环境温度和湿度。此外，必须保护它免受十二指肠中胃液和胆汁的破坏作用。该产品应容易并立即溶解在动物的口中，而不是被人工和/或空中诱饵分配破坏。我们建议将两种技术联合收割机结合起来，制备一种新型狂犬病疫苗，该疫苗应具有良好的产量，具有成本效益，在环境温度下应稳定，在穿过胃和十二指肠时更稳定。汽化保存（PBV）是由PI发明的，拥有一项正在申请的专利，并将敏感的生物制品固定在“玻璃状态”，因此它们在环境温度下是稳定的。藻酸盐凝胶包封已在工业中使用多年，以保护疫苗免受GI系统的损害。我们建议使用PBV干燥海藻酸钠凝胶微球包裹的新鲜狂犬病疫苗。具体目标是：（1）。制定采用PBV技术干燥动物用狂犬病疫苗的方案。证明干燥保存疫苗在37 ℃和60 ℃下的稳定性2）开发海藻酸盐凝胶微球（平均直径约100？）由病毒颗粒和保存溶液组成，通过从颗粒中浸出或泄漏，病毒损失最小（小于10%）。3.）第三章采用PBV技术制备海藻酸钠微球包封狂犬病疫苗的干燥方案。证明干燥保存疫苗在37 ℃和60 ℃下的稳定性。需要在60 ℃下的短期稳定性，以将疫苗包埋在可食用的氢化油或脂肪中，以确保免受环境湿度的影响。该项目的长期目标是生产在野外稳定的诱饵，将被野生动物食用，并且不会在胃肠道中被破坏，因此它将在肠道中产生强烈的免疫反应。UST将与CDC和Merial Inc.合作。他们将提供疫苗并进行生存力分析。公共卫生相关性：狂犬病每年造成的死亡人数估计在4万至7万之间。在美国，狂犬病的生活成本很高，而且还在增长，每年超过3亿美元。虽然狂犬病疫苗已用于家畜多年，但直到最近才开发出这种预防措施来控制野生动物的狂犬病。开发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，可以让野生动物接种疫苗，使它们不会感染狂犬病，从而有助于根除这种疾病。

项目成果

Assessment of the immunogenicity of rabies vaccine preserved by vaporization and delivered to the duodenal mucosa of gray foxes (Urocyon cinereoargenteus).

评估通过汽化保存并递送至灰狐（Urocyon cinereoargenteus）十二指肠粘膜的狂犬病疫苗的免疫原性。

• DOI: 10.2460/ajvr.78.6.752
• 发表时间: 2017
• 期刊: American journal of veterinary research
• 影响因子: 1
• 作者: Smith,ToddG;Wu,Xianfu;Ellison,JamesA;Wadhwa,Ashutosh;Franka,Richard;Langham,GregoryL;Skinner,BriannaL;Hanlon,CathleenA;Bronshtein,VictorL
• 通讯作者: Bronshtein,VictorL