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含有AMA1抗原片段的重组嵌合蛋白的免疫原性和免疫保护活性

The Immunogenic and Immunoprotective Activities of Recombinant Chimeric Proteins Containing AMA1 Antigen Fragments.

作者信息

Gatkowska Justyna, Dzitko Katarzyna, Ferra Bartłomiej Tomasz, Holec-Gąsior Lucyna, Kawka Malwina, Dziadek Bożena

机构信息

Department of Molecular Microbiology, Faculty of Biology and Environmental Protection, University of Lodz, 90-237 Łódź, Poland.

Department of Molecular Biotechnology and Microbiology, Faculty of Chemistry, Gdańsk University of Technology, 80-233 Gdańsk, Poland.

出版信息

Vaccines (Basel). 2020 Dec 2;8(4):724. doi: 10.3390/vaccines8040724.

Abstract

Toxoplasmosis, one of the most common parasitoses worldwide, is potentially dangerous for individuals with a weakened immune system, but specific immunoprophylaxis intended for humans is still lacking. Thus, efforts have been made to create an efficient universal vaccine for both animals and humans to overcome the shortcomings of currently used treatment methods and protect all hosts against toxoplasmosis. The current work represents a relatively new approach to vaccine development based on recombinant chimeric antigens. In the present research, three tetravalent chimeric proteins containing different portions of the parasite's AMA1 antigen-AMA1-SAG2-GRA1-ROP1 (ASGR), AMA1-SAG2-GRA1-ROP1 (ASGR) and AMA1-SAG2-GRA1-ROP1 (ASGR)-were tested for their immunogenic and immunoprotective capacities. All tested proteins were immunogenic, as evidenced by the triggering of specific humoral and cellular immune responses in vaccinated C3H/HeOuJ mice, defined by the production of specific IgG (IgG1/IgG2a) antibodies in vivo and synthesis of key Th1/Th2 cytokines by lysate antigen-stimulated splenocytes in vitro. Although all tested preparations provided partial protection against chronic toxoplasmosis in immunized and -challenged mice, the intensity of the generated immunoprotection depended on the fragment of the AMA1 antigen incorporated into the chimeric antigen's structure.

摘要

弓形虫病是全球最常见的寄生虫病之一,对免疫系统较弱的个体有潜在危险,但仍缺乏针对人类的特异性免疫预防措施。因此,人们一直在努力研发一种对动物和人类都有效的通用疫苗,以克服目前治疗方法的缺点,并保护所有宿主免受弓形虫病的侵害。目前的工作代表了一种基于重组嵌合抗原的相对较新的疫苗开发方法。在本研究中,测试了三种含有寄生虫AMA1抗原不同部分的四价嵌合蛋白——AMA1-SAG2-GRA1-ROP1(ASGR)、AMA1-SAG2-GRA1-ROP1(ASGR)和AMA1-SAG2-GRA1-ROP1(ASGR)——的免疫原性和免疫保护能力。所有测试蛋白都具有免疫原性,接种C3H/HeOuJ小鼠体内产生特异性IgG(IgG1/IgG2a)抗体以及体外裂解物抗原刺激的脾细胞合成关键Th1/Th2细胞因子所定义的特异性体液和细胞免疫反应的触发证明了这一点。尽管所有测试制剂都为免疫和攻击的小鼠提供了对慢性弓形虫病的部分保护,但产生的免疫保护强度取决于掺入嵌合抗原结构中的AMA1抗原片段。

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