Potent Rabies Vaccines for Free Ranging Carnivores

狂犬病不仅是一个公共卫生问题，每年导致40,000多人死亡 在世界范围内也造成了巨大的经济负担。仅在美国，每年用于控制、治疗和预防狂犬病的资金就超过10亿美元。在发展中国家，流浪狗是狂犬病的主要携带者。然而，在北美，野生动物物种，特别是浣熊和臭鼬，占所有狂犬病病例的90%以上。口服免疫是控制和根除流浪狗和野生动物狂犬病最有效的方法。不幸的是，现有的口服狂犬病疫苗对狗和臭鼬的免疫力不足，在本研究的初始阶段，人们通过不同的基因操作开发了狂犬病重组病毒，旨在消除致病性和增强免疫原性。这项研究项目的第二阶段的具体目标是扩大这些新开发的狂犬病疫苗在实验室啮齿动物和目标动物(浣熊和臭鼬)中的安全性和有效性测试，并选择一种将为其准备和表征主要种子库的菌株，并为商业生产开发生物反应器工艺。 建议的商业应用： 美国农业部和APHIS，WS提议扩大口服狂犬病疫苗接种计划，旨在阻止狂犬病的蔓延，并在美国选定的州减少狂犬病病例的发生率。如果这项研究能够提供一种更安全、更有效和更具成本效益的口服狂犬病疫苗，新疫苗可能会取代目前在该项目中使用的V-RG疫苗。

Rabies is not only a public health problem that causes more than 40,000 human deaths per year worldwide but also causes a tremendous economic burden. In the USA alone, more than one billion dollars are spent annually for control, treatment, and prevention of rabies. In developing countries stray dogs are the major carriers of rabies. However, in North America wildlife species, in particular raccoons and skunks, account for more than 90% of all rabies cases. Oral immunization is the most effective method to control and eradicate rabies in stray dogs and wildlife. Unfortunately, the currently available oral rabies vaccine induces insufficient immunity in dogs and skunks, in the initial phase of this research rabies recombinant viruses have been developed by distinct genetic manipulations designed to eliminate pathogenicity and augment immunogenicity. The specific phase II objectives of this research project are to extend safety and efficacy testing of these newly developed rabies vaccines in laboratory rodents and target animals (raccoon and skunk), and to choose a strain for which a master seed stock will be prepared and characterized and a bioreactor process developed for commercial production. PROPOSED COMMERCIAL APPLICATION: The USDA and APHIS, WS are proposing to expand the oral rabies vaccination program designed to stop the advance of rabies and reduce the incidence of rabies cases in selected states in the US. If this research is able to provide a safer, more potent and cost-effective oral rabies vaccine, the new vaccine could potentially supplant the currently used V-RG vaccine in this program.