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重组菌苗疫苗对牛肉毒梭菌病的保护效力。

Protective efficacy of recombinant bacterin vaccine against botulism in cattle.

机构信息

Centro de Desenvolvimento Tecnológico, Núcleo de Biotecnologia, Universidade Federal de Pelotas, Pelotas, Rio Grande do Sul, CEP 96160-000, Brazil.

Instituto de Medicina Veterinária, Universidade Federal do Pará, Castanhal, Pará, CEP 68740-970, Brazil.

出版信息

Vaccine. 2020 Mar 4;38(11):2519-2526. doi: 10.1016/j.vaccine.2020.01.089. Epub 2020 Feb 6.

Abstract

Botulism is a paralytic disease caused by the intoxication of neurotoxins produced by Clostridium botulinum. Among the seven immunologically distinct serotypes of neurotoxins (BoNTs A - G), serotypes C and D, or a chimeric fusion termed C/D or D/C, are responsible for animal botulism. The most effective way to prevent botulism in cattle is through vaccination; however, the commercially available vaccines produced by detoxification of native neurotoxins are time-consuming and hazardous. To overcome these drawbacks, a non-toxic recombinant vaccine was developed as an alternative. In this study, the recombinant protein vaccine was produced using an Escherichia coli cell-based system. The formaldehyde-inactivated E. coli is able to induce 7.45 ± 1.77 and 6.6 ± 1.28 IU/mL neutralizing mean titers against BoNTs C and D in cattle, respectively, determined by mouse neutralization bioassay, and was deemed protective by the Brazilian legislation. Moreover, when the levels of anti-BoNT/C and D were compared with those achieved by the recombinant purified vaccines, no significant statistical difference was observed. Cattle vaccinated with the commercial vaccine developed 1.33 and 3.33 IU/mL neutralizing mean titers against BoNT serotypes C and D, respectively. To the best of our knowledge, this study is the first report on recombinant E. coli bacterin vaccine against botulism. The vaccine was safe and effective in generating protective antibodies and, thus, represents an industry-friendly alternative for the prevention of cattle botulism.

摘要

肉毒中毒是一种由肉毒梭菌产生的神经毒素中毒引起的麻痹性疾病。在七种免疫上不同的神经毒素血清型(BoNTs A-G)中,血清型 C 和 D 或称为 C/D 或 D/C 的嵌合融合体负责动物肉毒中毒。预防牛肉毒中毒最有效的方法是通过接种疫苗;然而,通过脱毒天然神经毒素生产的市售疫苗既耗时又危险。为了克服这些缺点,开发了一种无毒的重组疫苗作为替代品。在这项研究中,使用基于大肠杆菌细胞的系统生产了重组蛋白疫苗。甲醛灭活的大肠杆菌能够诱导牛分别产生 7.45±1.77 和 6.6±1.28 IU/mL 的中和平均滴度,针对 BoNT C 和 D,通过小鼠中和生物测定确定,并且被巴西立法认为具有保护作用。此外,当比较抗 BoNT/C 和 D 的水平与重组纯化疫苗所达到的水平时,没有观察到显著的统计学差异。用商业疫苗接种的牛对 BoNT 血清型 C 和 D 分别产生 1.33 和 3.33 IU/mL 的中和平均滴度。据我们所知,这是第一项关于针对肉毒中毒的重组大肠杆菌菌苗的研究。该疫苗在产生保护性抗体方面是安全有效的,因此是预防牛肉毒中毒的一种对行业友好的替代方案。

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