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抗Bestrophin抗体对实验性丝虫病的治疗效果:免疫学、免疫信息学及免疫模拟研究

Therapeutic Efficacy of Anti-Bestrophin Antibodies against Experimental Filariasis: Immunological, Immune-Informatics and Immune Simulation Investigations.

作者信息

Das Nabarun Chandra, Ray Anindya Sundar, Bayry Jagadeesh, Mukherjeee Suprabhat

机构信息

Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University, Asansol 713340, West Bengal, India.

Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Sorbonne Universités, Université de Paris, F-75006 Paris, France.

出版信息

Antibodies (Basel). 2021 Apr 17;10(2):14. doi: 10.3390/antib10020014.

DOI:10.3390/antib10020014
PMID:33920596
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8167583/
Abstract

Lymphatic filariasis (LF) is a debilitating parasitic disease caused by filarial parasites and it is prevalent across the underprivileged population throughout the globe. The inadequate efficacy of the existing treatment options has provoked the conception of alternative strategies, among which immunotherapy is steadily emerging as a promising option. Herein, we demonstrate the efficacy of an antibody-based immunotherapeutic approach in an experimental model of filariasis, i.e., Wistar rat infected with (a model filarial parasite). The polyclonal antibodies were raised against filarial surface antigen bestrophin protein (FSAg) in mice using the purified FSAg. The adoptive transfer of anti-FSAg antibody-containing serum resulted in the significant reduction of parasite burden in filaria-infected rats. Intriguingly, anti-FSAg sera-treated animals also displayed a reduction in the level of proinflammatory cytokines as compared to the infected but untreated group. Furthermore, our in silico immunoinformatics data revealed eight B-cell epitopes and several T-cell epitopes in FSAg and these epitopes were linked to form a refined antigen in silico. The immune simulation suggested IgM and IgG1 as the predominant immunoglobulins induced in response to FSAg. Taken together, our experimental and simulation data collectively indicated a therapeutic potential of anti-FSAg sera against LF.

摘要

淋巴丝虫病(LF)是一种由丝虫寄生虫引起的使人衰弱的寄生虫病,在全球贫困人群中普遍存在。现有治疗方案的疗效不足促使人们构想替代策略,其中免疫疗法正逐渐成为一种有前景的选择。在此,我们在丝虫病实验模型中,即感染了(一种模型丝虫寄生虫)的Wistar大鼠中,证明了基于抗体的免疫治疗方法的疗效。使用纯化的丝虫表面抗原最佳rophin蛋白(FSAg)在小鼠中产生针对该蛋白的多克隆抗体。含有抗FSAg抗体的血清的过继转移导致丝虫感染大鼠体内寄生虫负荷显著降低。有趣的是,与感染但未治疗的组相比,抗FSAg血清处理的动物还显示出促炎细胞因子水平的降低。此外,我们的计算机免疫信息学数据揭示了FSAg中的八个B细胞表位和几个T细胞表位,并且这些表位在计算机上被连接以形成一种优化的抗原。免疫模拟表明IgM和IgG1是针对FSAg诱导产生的主要免疫球蛋白。综上所述,我们的实验和模拟数据共同表明抗FSAg血清对淋巴丝虫病具有治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/34b5c58f93ba/antibodies-10-00014-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/0d2a2538642c/antibodies-10-00014-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/0e3b441ca5d3/antibodies-10-00014-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/efdf0c626ee9/antibodies-10-00014-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/34b5c58f93ba/antibodies-10-00014-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/0d2a2538642c/antibodies-10-00014-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/0e3b441ca5d3/antibodies-10-00014-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/efdf0c626ee9/antibodies-10-00014-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9ce/8167583/34b5c58f93ba/antibodies-10-00014-g004.jpg

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Infect Genet Evol. 2021 Jan;87:104633. doi: 10.1016/j.meegid.2020.104633. Epub 2020 Nov 9.
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