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脂质配方卡介苗作为结核病口服诱饵疫苗:疫苗稳定性、效力及对新西兰帚尾袋貂(Trichosurus vulpecula)的适口性

Lipid-formulated bcg as an oral-bait vaccine for tuberculosis: vaccine stability, efficacy, and palatability to brushtail possums (Trichosurus vulpecula) in New Zealand.

作者信息

Cross Martin L, Henderson Ray J, Lambeth Matthew R, Buddle Bryce M, Aldwell Frank E

机构信息

Centre for Innovation, University of Otago, Dunedin, New Zealand.

出版信息

J Wildl Dis. 2009 Jul;45(3):754-65. doi: 10.7589/0090-3558-45.3.754.

Abstract

Bovine tuberculosis (Tb), due to infection with virulent Mycobacterium bovis, represents a threat to New Zealand agriculture due to vectorial transmission from wildlife reservoir species, principally the introduced Australian brushtail possum (Trichosurus vulpecula). An oral-delivery wildlife vaccine has been developed to immunize possums against Tb, based on formulation of the human Tb vaccine (M. bovis BCG) in edible lipid matrices. Here BCG bacilli were shown to be stable in lipid matrix formulation for over 8 mo in freezer storage, for 7 wk under room temperature conditions, and for 3-5 wk under field conditions in a forest/pasture margin habitat (when maintained in weatherproof bait-delivery sachets). Samples of the lipid matrix were flavored and offered to captive possums in a bait-preference study: a combination of 10% chocolate powder with anise oil was identified as the most effective attractant/palatability combination. In a replicated field study, 85-100% of wild possums were shown to access chocolate-flavored lipid pellets, when baits were applied to areas holding approximately 600-800 possums/km(2). Finally, in a controlled vaccination/challenge study, chocolate-flavored lipid vaccine samples containing 10(8) BCG bacilli were fed to captive possums, which were subsequently challenged via aerosol exposure to virulent M. bovis: vaccine immunogenicity was confirmed, and protection was identified by significantly reduced postchallenge weight loss in vaccinated animals compared to nonvaccinated controls. These studies indicate that, appropriately flavored, lipid delivery matrices may form effective bait vaccines for the control of Tb in wildlife.

摘要

牛结核病(Tb)是由强毒力的牛分枝杆菌感染引起的,由于野生动物宿主物种(主要是引入的澳大利亚帚尾袋貂(Trichosurus vulpecula))的媒介传播,对新西兰农业构成威胁。基于将人用结核疫苗(牛分枝杆菌卡介苗)制成可食用脂质基质,已开发出一种口服野生动物疫苗,用于免疫袋貂预防结核病。在此研究中,卡介苗杆菌在脂质基质制剂中冷冻保存超过8个月、室温条件下保存7周以及在森林/牧场边缘栖息地的野外条件下(保存在防风雨诱饵投放小袋中)保存3 - 5周时均表现稳定。在一项诱饵偏好研究中,对脂质基质样品进行调味后提供给圈养袋貂:结果确定10%巧克力粉与茴芹油的组合是最有效的引诱剂/适口性组合。在一项重复的野外研究中,当诱饵应用于每平方公里约有600 - 800只袋貂的区域时,85% - 100%的野生袋貂会取食巧克力味脂质颗粒。最后,在一项对照疫苗接种/攻毒研究中,将含有10⁸ 卡介苗杆菌的巧克力味脂质疫苗样品喂给圈养袋貂,随后通过气溶胶暴露使其接触强毒力牛分枝杆菌进行攻毒:疫苗免疫原性得到证实,并且与未接种疫苗的对照相比,接种疫苗的动物在攻毒后体重减轻显著减少,从而确定了疫苗的保护作用。这些研究表明,经过适当调味的脂质递送基质可能形成有效的诱饵疫苗,用于控制野生动物的结核病。

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