探索大肠杆菌外膜囊泡作为研制恰加斯病疫苗工具的性能。

IF 2.5 4区 医学 Q2 PARASITOLOGY
María Elisa Vázquez, Andrea Cecilia Mesías, Leonardo Acuña, Joseph Spangler, Brenda Zabala, Cecilia Parodi, Meghna Thakur, Eunkeu Oh, Scott Allan Walper, Cecilia Pérez Brandán
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引用次数: 1

摘要

背景:疫苗开发是一项艰苦的工艺,其中必须确定至少两个主要组成部分:高度免疫原性抗原和合适的递送方法。因此,这些元素的相互作用可能引发所需的免疫反应,以应对具有持久保护能力的目标病原体。目的:在这里,我们评估大肠杆菌球形蛋白脂质体(称为外膜囊泡(OMVs))作为具有天然佐剂能力的颗粒和抗原载体结构的特性,以组装一种创新的恰加斯病预防性疫苗。方法:采用含Tc24克氏锥虫抗原的工程质粒对大肠杆菌进行基因操作。目的是诱导omv的释放,omv表面显示寄生虫蛋白。研究结果:作为原理证明,我们观察到,在低免疫剂量下,天然omv以及携带克氏t病毒抗原的omv能够引发轻微但功能性的体液反应。值得注意的是,与未免疫组相比,本地接种了omv疫苗的动物在致命攻击中存活下来,并显示出轻微的寄生虫血症值,这表明可能涉及先天训练免疫机制。主要结论:这些结果为进一步研究以先天免疫激活作为额外免疫靶点的新载体策略的设计开辟了范围,并冒险寻找可用于优化疫苗开发的omv的替代形式。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.

Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.

Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.

Exploring the performance of Escherichia coli outer membrane vesicles as a tool for vaccine development against Chagas disease.

Background: Vaccine development is a laborious craftwork in which at least two main components must be defined: a highly immunogenic antigen and a suitable delivery method. Hence, the interplay of these elements could elicit the required immune response to cope with the targeted pathogen with a long-lasting protective capacity.

Objectives: Here we evaluate the properties of Escherichia coli spherical proteoliposomes - known as outer membrane vesicles (OMVs) - as particles with natural adjuvant capacities and as antigen-carrier structures to assemble an innovative prophylactic vaccine for Chagas disease.

Methods: To achieve this, genetic manipulation was carried out on E. coli using an engineered plasmid containing the Tc24 Trypanosoma cruzi antigen. The goal was to induce the release of OMVs displaying the parasite protein on their surface.

Findings: As a proof of principle, we observed that native OMVs - as well as those carrying the T. cruzi antigen - were able to trigger a slight, but functional humoral response at low immunization doses. Of note, compared to the non-immunized group, native OMVs-vaccinated animals survived the lethal challenge and showed minor parasitemia values, suggesting a possible involvement of innate trained immunity mechanism.

Main conclusion: These results open the range for further research on the design of new carrier strategies focused on innate immunity activation as an additional immunization target and venture to seek for alternative forms in which OMVs could be used for optimizing vaccine development.

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来源期刊
CiteScore
5.00
自引率
3.60%
发文量
91
审稿时长
3-8 weeks
期刊介绍: Memórias do Instituto Oswaldo Cruz is a journal specialized in microbes & their vectors causing human infections. This means that we accept manuscripts covering multidisciplinary approaches and findings in the basic aspects of infectious diseases, e.g. basic in research in prokariotes, eukaryotes, and/or virus. Articles must clearly show what is the main question to be answered, the hypothesis raised, and the contribution given by the study. Priority is given to manuscripts reporting novel mechanisms and general findings concerning the biology of human infectious prokariotes, eukariotes or virus. Papers reporting innovative methods for diagnostics or that advance the basic research with these infectious agents are also welcome. It is important to mention what we do not publish: veterinary infectious agents research, taxonomic analysis and re-description of species, epidemiological studies or surveys or case reports and data re-analysis. Manuscripts that fall in these cases or that are considered of low priority by the journal editorial board, will be returned to the author(s) for submission to another journal.
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