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

基本信息

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
项目类别：
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

项目摘要

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）：狂犬病是由中枢神经系统病毒感染引起的一种急性和致命疾病，最常见于被感染（狂热的）动物（例如，蝙蝠，浣熊，臭鼬，臭鼬，狐狸）散布的。，雪貂，猫或狗）。每年狂犬病造成的死亡人数估计在40,000-70,000之间。与许多人畜共患病相比，保护人类的唯一方法是消除动物储层中的疾病。肠胃外狂犬病疫苗接种对拥有的狗和其他宠物是可行的，而野生动物和流浪动物需要口服疫苗接种，在食物或诱饵中输送狂犬病疫苗。目前，大约15个州为野生动物分发可食用的狂犬病疫苗，以消除这种疾病。这些疫苗的问题在于它们在环境条件下不稳定，并且在动物的胃肠道（GI）系统中很容易破坏。非常需要针对动物的新口腔狂犬病疫苗输送系统。必须保护疫苗免受阳光，高环境温度和湿度的保护。另外，必须保护它免受十二指肠胃汁和胆汁的破坏作用。该产品应轻易，立即溶解在动物的口腔中，而不是通过手动和/或空中诱饵分布破坏。我们建议将两种技术结合起来，以准备一种新型的狂犬病疫苗，该疫苗应该具有良好的产量，具有成本效益，并且应该在环境温度下保持稳定，并且更稳定地穿越胃和十二指肠。 PI发明了通过汽化（PBV）保存（PBV），具有待处理的专利，并将敏感生物学固定在“玻璃状态”中，因此它们在环境温度下稳定。藻酸盐凝胶封装已在该行业使用了几年，以保护疫苗免受GI系统损害。我们建议使用PBV来干燥藻类凝胶微球中的新鲜狂犬病疫苗。具体目的是：1。）制定使用PBV技术干燥动物狂犬病疫苗的方案。证明在37oC和60oc2处干燥的保留疫苗的稳定性。通过从颗粒中浸出或泄漏。 3.）制定使用PBV技术封装在藻酸盐微球中的狂犬病疫苗干燥的方案。证明在37oC和60oC处干燥的疫苗的稳定性。需要在60oC处进行短期稳定性，以将疫苗夹在可食用的氢化油或脂肪中，以确保防止环境湿度。该项目的远距离目标是产生在野外稳定的诱饵，将被野生动物食用，并且不会在胃肠道中破坏，因此它将在肠中产生强烈的免疫反应。 UST将与CDC和Merial Inc.合作，谁将提供疫苗并执行生存力分析。公共卫生相关性：狂犬病每年的死亡人数估计在40,000-70,000之间。美国与狂犬病的生活成本很高，而且增长，每年超过3亿美元。尽管狂犬病疫苗已用于家畜多年，但直到最近才制定了这种预防措施来控制野生动植物的狂犬病。诱饵的开发将嵌入食用氢化油中的稳定狂犬病疫苗，从而保护疫苗免受元素的影响，包括阳光，温度，湿度和胃汁，可以允许对野生动物进行疫苗接种，从而无法接受狂犬病，因此可以允许疫苗帮助消除疾病。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

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