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: 8000516
• 负责人: Victor Bronshtein
• 金额: $ 51.18万
• 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 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8000516
• 关键词: Achievement; Acids; Affect; Africa; Agreement; Alginates; Americas; Animal Model; Animals; Anthrax disease; Antigens; Asia; Attenuated; Attenuated Vaccines; Bacteria; Bile Acids; Bile fluid; Biological Preservation; Bite; Brothers; Calcium; Canis familiaris; Carbohydrates; Cell Nucleus; Centers for Disease Control and Prevention (U.S.); Cessation of life; Charge; Chemicals; Chiroptera; Cold Chains; Collaborations; Consumption; Coyotes; DNA Vaccines; Data; Developing Countries; Development; Disease; Disease Vectors; Dog Bite; Domestic Animals; Dose; Drops; Drug Formulations; Duodenum; Eating; Economic Burden; Economics; Elements; Encapsulated; Enteral; Environment; Environmental Protection; Enzymes; Europe; Evaluation; Fatty acid glycerol esters; Felis catus; Ferrets; Flavoring; Food; Food Supply; Foxes; Freeze Drying; Freezing; Funding; Future; Gastric Juice; Gastrointestinal tract structure; Gel; Glass; Glycoproteins; Goals; Heating; High temperature of physical object; Hour; Human; Humidity; Hydrogels; Immune response; Immunization; Intestinal Mucosa; Intestines; Legal patent; Licensing; Life; Liquid substance; Listeria; Living Costs; Manuals; Mastication; Measles; Measures; Meat; Mephitidae; Methods; Microspheres; Modeling; Mucous Membrane; Nitrogen; Oils; Oral; Oral cavity; Pharyngeal structure; Phase; Plastics; Play; Polymers; Population; Powder dose form; Preparation; Preventive; Probiotics; Production; Public Health; RNA Viruses; Rabies; Rabies Vaccines; Rabies virus; Raccoons; Refrigeration; Research; Role; Russia; Saliva; Salmonella; Shapes; Small Intestines; Smallpox; Solutions; Stomach; Sunlight; Suspension substance; Suspensions; System; Technology; Temperature; Testing; Time; Transportation; United States National Institutes of Health; Vaccinated; Vaccination; Vaccine Design; Vaccines; Vaccinia; Vaccinia virus; Variant; Viral Vaccines; Virus; Waxes; Wild Animals; Yellow Fever Vaccine; Zoonoses; base; capsule; commercialization; crosslink; design; falls; feral; innovation; interest; novel; novel vaccines; oral vaccine; particle; pet animal; phase 1 study; phase 2 study; phase 3 study; positional cloning; public health relevance; rabies virus glycoprotein G; success; user-friendly; vaccine delivery; vaccine efficacy; vaporization

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.

描述（由申请人提供）：狂犬病是一种致命的疾病，估计每年造成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）的咬伤和唾液传播。口服诱饵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，犬科动物（狗、狐狸、土狼）是人类疾病的主要传播媒介，它们不咀嚼食物或诱饵；相反，它会吞咽，导致疫苗在胃酸中被破坏。