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（由适用提供）：狂犬病是一种致命疾病，估计每年造成40-7万人死亡。它通常是由被感染的野生动物或野性动物（例如蝙蝠，浣熊，臭鼬，狐狸，狐狸，雪貂，猫或狗）的咬伤和唾液传播的。诱饵中的口服疫苗与咀嚼食物的动物成功，从而使疫苗诱饵与口腔和喉咙粘膜接触以引起免疫反应。但是，犬科种（狗，狐狸，土狼）是人类疾病的主要媒介，不会咀嚼食物或诱饵。相反，它吞下了导致疫苗在胃酸中破坏的疫苗。 对于我们的第一阶段项目，我们组合了两种技术，以准备一种新型的兔疫苗，旨在在环境温度和HARMSH环境中稳定，例如在通往小肠的稳定性酸和胆汁分泌过程中，我们建议它可以通过雄蕊Mucosa免疫动物。 PI的专利待限制“通过汽化保存”（PBV）技术将固定在“玻璃状态”中的敏感生物学固定在“玻璃状态”中，因此在环境温度下它们的稳定性已被算法凝胶封装用于保护疫苗，以保护疫苗免受热和化学损害。 UST利用PBV来干燥两种藻酸盐包含的疫苗VRG（基于疫苗）和ERA（基于狂犬病）。我们超过了在60°C的1小时平衡期间的疫苗稳定性的原始目标规格，在37°C下2周后。 II期项目的具体目的是：1）优化封装在藻酸盐凝胶微球中的干狂犬疫苗的公式。 2）配方狂犬病疫苗诱饵核核（RVABN）装有VRG和ERA疫苗。 3）评估疫苗产物在动物研究中的效率，特别是狐狸和狗，以应对狂犬病挑战。 该项目的远距离目标是为在野外稳定的诱饵中分泌的狂犬病生产口服疫苗。曾经被野生动物食用的这种疫苗不会在胃肠道中破坏，并且会在肠中产生强烈的免疫反应。 UST将与CDC和Merial Ltd.合作，他们将提供疫苗并帮助进行动物研究。 公共卫生相关性：每年狂犬病造成的死亡人数估计在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。尽管狂犬病疫苗已经用于家畜多年，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。诱饵的发展将嵌入可食用的氢化油中，从而保护疫苗免受元素的影响，包括阳光，温度，湿度和胃汁，可以允许野生动物的疫苗，因此它们没有狂犬病，因此可以帮助消除这种疾病。