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用掺入免疫刺激复合物(iscoms)的克氏锥虫前鞭毛体抗原进行免疫接种可保护小鼠免受致死性攻击。

Immunization with Trypanosoma cruzi epimastigote antigens incorporated into iscoms protects against lethal challenge in mice.

作者信息

Araujo F G, Morein B

机构信息

Research Institute, Palo Alto Medical Foundation, California 94301.

出版信息

Infect Immun. 1991 Sep;59(9):2909-14. doi: 10.1128/iai.59.9.2909-2914.1991.

DOI:10.1128/iai.59.9.2909-2914.1991
PMID:1908826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC258112/
Abstract

An immunoglobulin G3 monoclonal antibody obtained by immunizing mice with a cell membrane preparation of epimastigotes of Trypanosoma cruzi was shown to agglutinate live epimastigotes, lyse blood-form trypanosomes, and partially protect mice by passive transfer. The main antigens recognized by the monoclonal antibody were located in the flagella of epimastigotes and blood-form trypanosomes. Antigens of epimastigotes, purified by affinity chromatography with the monoclonal antibody, were shown to be highly glycosylated and revealed a wide band with an Mr between 45,000 and 68,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Immunization of mice with a small concentration of the affinity purified antigens incorporated into an antigen delivery system prepared with Quil A (Isotec AB, Lulea, Sweden), a saponin derivative, induced strong antibody and cell-mediated immune responses and protected 100% of the immunized animals against death due to challenge with 100 100% lethal doses of blood form trypanosomes. Protection was due to the use of the antigen delivery system, since mice immunized with equal concentrations of antigens alone or in combination with saponin had 100% mortality. The results suggest that small concentrations of epimastigote antigens obtained by biochemical methods and incorporated into the proper antigen delivery system may serve as a vaccine against Chagas' disease.

摘要

用克氏锥虫前鞭毛体细胞膜制剂免疫小鼠获得的一种免疫球蛋白G3单克隆抗体,已显示出能凝集活的前鞭毛体、裂解血液型锥虫,并通过被动转移部分保护小鼠。该单克隆抗体识别的主要抗原位于前鞭毛体和血液型锥虫的鞭毛中。用该单克隆抗体通过亲和层析纯化的前鞭毛体抗原,显示出高度糖基化,在十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和免疫印迹中呈现出一条分子量在45,000至68,000之间的宽带。用掺入由皂苷衍生物Quil A(瑞典吕勒奥的Isotec AB公司)制备的抗原递送系统中的低浓度亲和纯化抗原免疫小鼠,诱导出强烈的抗体和细胞介导的免疫反应,并保护100%的免疫动物免受100个100%致死剂量的血液型锥虫攻击致死。这种保护作用归因于抗原递送系统的使用,因为单独用等量抗原或与皂苷联合免疫的小鼠有100%的死亡率。结果表明,通过生化方法获得并掺入适当抗原递送系统的低浓度前鞭毛体抗原可能用作抗恰加斯病的疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/a273fa6ab2d1/iai00045-0067-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/d21ccb1e044d/iai00045-0066-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/97762430744e/iai00045-0067-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/a273fa6ab2d1/iai00045-0067-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/d21ccb1e044d/iai00045-0066-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/97762430744e/iai00045-0067-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7e52/258112/a273fa6ab2d1/iai00045-0067-b.jpg

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本文引用的文献

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Chagas disease in Mexico.墨西哥的恰加斯病。
Parasitol Today. 1988 Dec;4(12):348-52. doi: 10.1016/0169-4758(88)90004-x.
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Monoclonal antibodies to stages of Trypanosoma cruzi: characterization and use for antigen detection.针对克氏锥虫各阶段的单克隆抗体:特性及用于抗原检测
Infect Immun. 1982 Jul;37(1):344-9. doi: 10.1128/iai.37.1.344-349.1982.
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Resistance against Trypanosoma cruzi associated to anti-living trypomastigote antibodies.与抗活锥鞭毛体抗体相关的克氏锥虫抗性。
纯副鞭毛杆蛋白可保护小鼠免受克氏锥虫感染。
Infect Immun. 1995 Jan;63(1):122-5. doi: 10.1128/iai.63.1.122-125.1995.
J Immunol. 1982 May;128(5):2009-12.
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Characterization of stages and strains of Trypanosoma cruzi by analysis of cell membrane components.通过分析细胞膜成分对克氏锥虫的阶段和菌株进行鉴定。
J Immunol. 1981 Sep;127(3):855-9.
5
Iscom, a novel structure for antigenic presentation of membrane proteins from enveloped viruses.免疫刺激复合物(ISCOM),一种用于包膜病毒膜蛋白抗原呈递的新型结构。
Nature. 1984;308(5958):457-60. doi: 10.1038/308457a0.
6
Resistance to Trypanosoma cruzi induced by immunization with antigens isolated by affinity chromatography.通过亲和层析分离的抗原免疫诱导产生的对克氏锥虫的抗性。
Braz J Med Biol Res. 1984;17(2):157-64.
7
Use of antigen preparations of the amastigote stage of Trypanosoma cruzi in the serology of Chagas' disease.克氏锥虫无鞭毛体阶段抗原制剂在恰加斯病血清学中的应用。
Am J Trop Med Hyg. 1984 May;33(3):362-71. doi: 10.4269/ajtmh.1984.33.362.
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Surface antigens of metacyclic trypomastigotes of Trypanosoma cruzi.克氏锥虫循环后期锥鞭毛体的表面抗原
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