Formulation of Ambient Temperature and Humidity Stable Rabies Vaccines

环境温度和湿度稳定的狂犬病疫苗的配制

• 批准号: 8088192
• 负责人: Victor Bronshtein
• 金额: $ 63.4万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8088192
• 关键词: Acids; Alginates; Americas; Animals; Bile Acids; Biological; Biological Preservation; Bite; Canis familiaris; Cell Nucleus; Centers for Disease Control and Prevention (U.S.); Cessation of life; Chemicals; Chiroptera; Coyotes; Development; Disease; Disease Vectors; Domestic Animals; Drug Formulations; Eating; Elements; Encapsulated; Environment; Felis catus; Ferrets; Food; Foxes; Gastric Juice; Gastrointestinal tract structure; Gel; Glass; Goals; Health; Heating; Hour; Human; Humidity; Immune response; Intestinal Mucosa; Intestines; Legal patent; Living Costs; Measures; Mephitidae; Microspheres; Mucous Membrane; Oils; Oral cavity; Pharyngeal structure; Phase; Preventive; Rabies; Rabies Vaccines; Raccoons; Saliva; Small Intestines; Stomach; Sunlight; Technology; Temperature; Vaccination; Vaccine Design; Vaccines; Vaccinia; Vaccinium; Wild Animals; base; feral; novel; oral vaccine; 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（申请人提供）：狂犬病是一种致命的疾病，估计每年造成4万至7万人死亡。它最常通过被感染的野生或野生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）。在诱饵中的口服疫苗已经成功地用于咀嚼食物的动物，从而允许疫苗诱饵与口腔和咽喉粘膜接触以引发免疫应答。然而，犬科动物（狗，狐狸，土狼），这种疾病对人类的主要载体，不咀嚼他们的食物或诱饵;相反，它吞下导致疫苗在胃酸中被破坏。 对于我们的第一阶段项目，我们结合了两种技术来制备一种新型的狂犬病疫苗，该疫苗旨在在环境温度和恶劣环境下保持稳定，例如在通过胃酸和胆汁分泌到达小肠的过程中，我们建议它可以通过肠粘膜免疫动物。PI正在申请专利的“汽化保存”（PBV）技术将敏感生物制品固定在“玻璃状态”，使其在环境温度下保持稳定，该技术已与藻酸盐凝胶封装一起使用，以保护疫苗免受热和化学损伤。UST利用PBV干燥保存两种藻酸盐包封的疫苗VRG（基于牛痘）和ERA（基于狂犬病）。我们在60 ℃下平衡1小时和37 ℃下平衡2周后超过了疫苗稳定性的原始目标质量标准。 二期工程的具体目标是：1）优化海藻酸钠凝胶微球冻干狂犬病疫苗的配方。2)配制填充有VRG和ERA疫苗的狂犬病疫苗动物诱饵核心（RVABN）。3)在动物研究中评价疫苗产品（特别是狐狸和犬）对抗狂犬病攻毒的有效性。 该项目的长期目标是生产一种口服狂犬病疫苗，该疫苗分泌在野外稳定的诱饵中。这种疫苗一旦被野生动物食用，不会在胃肠道内被破坏，会在肠道内产生强烈的免疫反应。UST将与CDC和Merial Ltd.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。