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缺失NcGRA7的寄生虫作为减毒活疫苗对小鼠新孢子虫感染的保护效力。

Protective efficacy of the NcGRA7-deficient parasite as a live attenuated vaccine against Neospora caninum infection in mice.

作者信息

Abdou Ahmed M, Nishikawa Yoshifumi

机构信息

National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan.

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt.

出版信息

J Vet Med Sci. 2025 May 1;87(5):472-480. doi: 10.1292/jvms.24-0460. Epub 2025 Mar 20.

Abstract

Live vaccination is the most protective method against bovine neosporosis, which is the major cause of bovine abortion globally. Here, the Neospora caninum parenteral strain Nc1 and NcGRA7-deficient N. caninum (NcGRA7KO), which is less virulent in mice, were evaluated as potential live vaccines. BALB/c mice were subcutaneously inoculated with high (1 × 10) or low (1 × 10) doses of tachyzoites. At high doses, Nc1-inoculated female mice presented decreased body weight gain and increased clinical signs and died before challenge infection with green fluorescent protein (GFP)-expressing Nc1 (Nc1-GFP), whereas NcGRA7KO-inoculated animals exhibited increased survival before and after challenge infection. Although inoculation of female mice with Nc1 or NcGRA7KO resulted in a lower brain parasite number of challenged Nc1-GFP than in noninoculated animals, the total brain parasite burden in NcGRA7KO-infected mice decreased compared with that in Nc1-infetced animals. At low dose of NcGRA7KO, increased survival rates of mice and lower total brain parasite number were observed compared with high dose of NcGRA7KO. In male mice, a significant lower brain parasite burden of Nc1-GFP was observed in both high and low doses of NcGRA7-inoculated mice, and the total parasite number in the brains of low dose of NcGRA7KO-inoculated animals was lower than that in the brains of high dose of NcGRA7KO-inoculated or noninoculated animals. In conclusion, these results suggest that NcGRA7KO parasites have potential for use as a live vaccine against N. caninum infection.

摘要

活疫苗接种是预防牛新孢子虫病最有效的方法,牛新孢子虫病是全球范围内牛流产的主要原因。在此,对犬新孢子虫亲本菌株Nc1和毒力较低的NcGRA7基因缺失的犬新孢子虫(NcGRA7KO)进行评估,看其是否可作为潜在的活疫苗。将BALB/c小鼠皮下接种高剂量(1×10)或低剂量(1×10)的速殖子。高剂量时,接种Nc1的雌性小鼠体重增加减少,临床症状加重,在感染表达绿色荧光蛋白(GFP)的Nc1(Nc1-GFP)进行攻毒感染前死亡,而接种NcGRA7KO的动物在攻毒感染前后的存活率均有所提高。尽管用Nc1或NcGRA7KO接种雌性小鼠后,攻毒的Nc1-GFP在脑中的寄生虫数量低于未接种动物,但与接种Nc1的动物相比,NcGRA7KO感染小鼠脑中的总寄生虫负荷有所降低。低剂量的NcGRA7KO与高剂量相比,小鼠存活率提高,脑中总寄生虫数量减少。在雄性小鼠中,高剂量和低剂量接种NcGRA7的小鼠中,Nc1-GFP在脑中的寄生虫负荷均显著降低,低剂量接种NcGRA7KO的动物脑中的总寄生虫数量低于高剂量接种NcGRA7KO或未接种动物。总之,这些结果表明,NcGRA7KO寄生虫有潜力用作预防犬新孢子虫感染的活疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f3f/12150866/d7d0b15ced79/jvms-87-5-472-g001.jpg

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