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展示刚地弓形虫顶膜抗原1的病毒样颗粒疫苗可诱导小鼠抵抗刚地弓形虫ME49感染。

Virus-like particle vaccine displaying Toxoplasma gondii apical membrane antigen 1 induces protection against T. gondii ME49 infection in mice.

作者信息

Kim Min-Ju, Lee Su-Hwa, Kang Hae-Ji, Chu Ki-Back, Park Hyunwoo, Jin Hui, Moon Eun-Kyung, Kim Sung Soo, Quan Fu-Shi

机构信息

Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

Health Park Co., Ltd, Seoul, 06627, Republic of Korea.

出版信息

Microb Pathog. 2020 Feb 22;142:104090. doi: 10.1016/j.micpath.2020.104090.

Abstract

Toxoplasmosis is an intracellular parasitic disease caused by the protozoa Toxoplasma gondii, which affects about half of the world's population. In spite of the strenuous endeavors, a T. gondii vaccine for clinical use remains unreported to date. In the present study, we generated virus-like particles (VLPs) containing T. gondii apical membrane antigen 1 (AMA1) and assessed its efficacy in a murine model. VLPs were characterized using western blot and TEM. T. gondii-specific IgG and IgA antibody responses in sera, germinal center B cell responses in spleen, brain cyst counts and their sizes were determined. Elevated T. gondii-specific IgG and IgA antibody responses were observed from the sera of AMA1 VLP-immunized mice. Immunization with AMA1 VLPs enhanced T. gondii-specific antibody-secreting cell responses and germinal center B cell responses upon antigen stimulation. Brain tissue analysis revealed that AMA1 VLP-immunization reduced cyst formation and its size compared to control. Also, VLP-immunized mice were less susceptible to body weight loss and displayed enhanced survival rate compared to the control group. Our results demonstrated that the immune response induced by T. gondii AMA1 VLPs confer partial protection against T. gondii infection and provides important insight into potential T. gondii vaccine design strategy.

摘要

弓形虫病是一种由原生动物刚地弓形虫引起的细胞内寄生虫病,全球约有一半人口受其影响。尽管付出了巨大努力,但迄今为止仍未报道有可用于临床的弓形虫疫苗。在本研究中,我们制备了含有弓形虫顶膜抗原1(AMA1)的病毒样颗粒(VLP),并在小鼠模型中评估了其功效。通过蛋白质免疫印迹和透射电子显微镜对VLP进行了表征。测定了血清中弓形虫特异性IgG和IgA抗体反应、脾脏中生发中心B细胞反应、脑囊肿数量及其大小。在AMA1 VLP免疫小鼠的血清中观察到弓形虫特异性IgG和IgA抗体反应升高。用AMA1 VLP免疫可增强抗原刺激后弓形虫特异性抗体分泌细胞反应和生发中心B细胞反应。脑组织分析显示,与对照组相比,AMA1 VLP免疫可减少囊肿形成及其大小。此外,与对照组相比,VLP免疫小鼠体重减轻较少,存活率提高。我们的结果表明,弓形虫AMA1 VLP诱导的免疫反应可对弓形虫感染提供部分保护,并为潜在的弓形虫疫苗设计策略提供了重要见解。

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