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用重组蛋白鸡尾酒疫苗接种的新生犊牛中,鸟分枝杆菌副结核亚种的组织定植减少。

Reduced tissue colonization of Mycobacterium avium subsp. paratuberculosis in neonatal calves vaccinated with a cocktail of recombinant proteins.

机构信息

USDA-ARS, National Animal Disease Center, Ames, IA 50010, United States.

USDA-ARS, National Animal Disease Center, Ames, IA 50010, United States.

出版信息

Vaccine. 2021 May 27;39(23):3131-3140. doi: 10.1016/j.vaccine.2021.04.051. Epub 2021 May 7.

Abstract

An increasing prevalence of paratuberculosis supports the need for new efficacious vaccines as an essential management tool. Two separate studies were performed in neonatal calves to evaluate the effectiveness of pooled recombinant Mycobacterium avium subsp. paratuberculosis (MAP) proteins (MAP1087, MAP1204, MAP1272c, MAP2077c) as a potential vaccine. In the first study vaccinated calves were immunized with 400 µg protein cocktail per dose, whereas the second study compared doses of 400 µg and 800 µg of protein cocktail, followed by challenge with live MAP for both vaccinated and nonvaccinated control calves 28 days post-vaccination. At the end of 12 months, tissue colonization with MAP was significantly reduced for the vaccinated calves compared to control animals. A higher dose of vaccine improved protection, with further reductions of MAP burden. Antigen-specific IFN-γ responses and serum antibody responses were similar regardless of vaccination, indicating exposure to MAP invoked conventional host immune responses. Host immunity differed due to vaccination, resulting in increased percentages of CD4+ T cells and B cells after stimulation of PBMCs with antigen. Interestingly, gene expression in PBMCs was similar for both control and vaccinated calves except for significant increases in IFN-γ, IL-12, and IL-17 expression observed in vaccinated calves. Vaccination with a cocktail of immunogenic recombinant MAP proteins was efficacious in reducing the level of infection and fecal shedding of neonatal calves and may be a potential tool for curtailing the spread of Johne's disease.

摘要

副结核病的流行率不断上升,支持需要新的有效疫苗作为重要的管理工具。在新生犊牛中进行了两项独立的研究,以评估混合重组禽分枝杆菌副结核亚种(MAP)蛋白(MAP1087、MAP1204、MAP1272c、MAP2077c)作为潜在疫苗的有效性。在第一项研究中,接种疫苗的犊牛每剂接受 400µg 蛋白混合物免疫,而第二项研究比较了 400µg 和 800µg 蛋白混合物剂量,然后在接种后 28 天对接种疫苗和未接种疫苗的对照犊牛用活 MAP 进行攻毒。在 12 个月结束时,与对照动物相比,接种疫苗的犊牛的组织中 MAP 定植明显减少。较高剂量的疫苗可提高保护效果,进一步降低 MAP 负担。无论接种与否,抗原特异性 IFN-γ 反应和血清抗体反应相似,表明 MAP 暴露引发了常规宿主免疫反应。由于接种疫苗,宿主免疫反应不同,导致在用抗原刺激 PBMC 后 CD4+T 细胞和 B 细胞的百分比增加。有趣的是,除了接种疫苗的犊牛中观察到 IFN-γ、IL-12 和 IL-17 表达显著增加外,PBMC 中的基因表达在对照和接种疫苗的犊牛中相似。用免疫原性重组 MAP 蛋白混合物进行疫苗接种可有效降低新生犊牛的感染水平和粪便脱落量,并可能成为遏制约翰氏病传播的潜在工具。

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