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缺失棒状体蛋白38(PruΔ)作为鼠模型中弓形虫病疫苗候选物的研究

Deletion of Rhoptry Protein 38 (PruΔ) as a Vaccine Candidate for Toxoplasmosis in a Murine Model.

作者信息

Wu Yayun, Zhou Zihui, Ying Zhu, Xu Ying, Liu Jing, Liu Qun

机构信息

National Animal Protozoa Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.

出版信息

Biomedicines. 2022 Jun 6;10(6):1336. doi: 10.3390/biomedicines10061336.

Abstract

Toxoplasmosis is a serious zoonotic disease that threatens human and animal health. Here, we evaluated the vaccine potential of the deletion of rhoptry protein 38 (PruΔ) through its pathogenicity and immunoprotective efficacy in mice. Mice inoculated intraperitoneally with 1 × 10, 2 × 10, or 4 × 10 PruΔ showed no visible signs, whereas mice inoculated with 1 × 10 parental Pru strain showed obvious wasting and bow-back, suggesting a significantly lower pathogenicity of PruΔ in mice. Vaccination with 1 × 10 PruΔ triggered a mixed Th1/Th2 response (Th1 response predominant), with higher IgG, IgG2a, and IgG1 levels in serum from week 3 to week 12, and a significant increase in IFN-γ, IL-12, and IL-10 in suspensions of splenocytes at 30 or 60 days post-immunization. All vaccinated mice survived when infected intraperitoneally with tachyzoites (RH, Pru, VEG, or TgcatBJ1) or when infected orally with cysts (Pru or ME49). The brain parasite burden during Pru tachyzoite, Pru cyst and ME49 cyst challenges were significantly reduced in vaccinated mice. The duration of immunization showed that vaccination with PruΔ could protect mice from challenge with different varied genotypes of strains against different routes of infection. Collectively, these findings indicate that PruΔ is an attenuated strain that provides long-term protective efficacy against acute or chronic toxoplasmosis in mice.

摘要

弓形虫病是一种严重的人畜共患病,威胁着人类和动物的健康。在此,我们通过评估缺失棒状体蛋白38(PruΔ)在小鼠体内的致病性和免疫保护效果,来评价其作为疫苗的潜力。腹腔注射1×10、2×10或4×10个PruΔ的小鼠未出现明显症状,而注射1×10个亲本Pru株的小鼠则出现明显消瘦和弓背现象,这表明PruΔ在小鼠体内的致病性显著降低。用1×10个PruΔ进行疫苗接种引发了混合的Th1/Th2反应(以Th1反应为主),在第3周至第12周血清中的IgG、IgG2a和IgG1水平较高,并且在免疫后30天或60天时脾细胞悬液中的IFN-γ、IL-12和IL-10显著增加。所有接种疫苗的小鼠在腹腔感染速殖子(RH、Pru、VEG或TgcatBJ1)或口服感染包囊(Pru或ME49)时均存活。在接种疫苗的小鼠中,Pru速殖子、Pru包囊和ME49包囊攻击期间的脑内寄生虫负荷显著降低。免疫持续时间表明,用PruΔ进行疫苗接种可以保护小鼠免受不同基因型菌株不同感染途径的攻击。总的来说,这些发现表明PruΔ是一种减毒株,可对小鼠急性或慢性弓形虫病提供长期保护效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b4/9220005/31ada9421241/biomedicines-10-01336-g001.jpg

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