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探索大肠杆菌外膜囊泡作为恰加斯病疫苗开发工具的性能。

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

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad Nacional de Salta, Instituto de Patología Experimental Dr Miguel Ángel Basombrío, Salta, Argentina.

US Naval Research Laboratory, Center for Bio/Molecular Science & Engineering, Washington, DC, United States of America.

出版信息

Mem Inst Oswaldo Cruz. 2023 May 22;118:e220263. doi: 10.1590/0074-02760220263. eCollection 2023.

Abstract

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.

摘要

背景

疫苗的开发是一项艰苦的工作,至少必须定义两个主要成分:高度免疫原性抗原和合适的传递方法。因此,这些元素的相互作用可以引发所需的免疫反应,以持久的保护能力应对靶向病原体。

目的

在这里,我们评估大肠杆菌球形脂膜囊 - 称为外膜囊泡(OMV) - 的特性,作为具有天然佐剂能力的颗粒和抗原载体结构,以组装一种用于恰加斯病的创新预防性疫苗。

方法

为了实现这一目标,使用含有 Tc24 克氏锥虫抗原的工程质粒对大肠杆菌进行了基因操作。目的是诱导释放表面显示寄生虫蛋白的 OMV。

发现

作为原理的证明,我们观察到天然 OMV - 以及携带 T. cruzi 抗原的 OMV - 能够在低免疫剂量下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,天然 OMV 疫苗接种的动物在致命挑战中存活下来,并显示出较低的寄生虫血症值,这表明先天训练免疫机制可能参与其中。

主要结论

这些结果为进一步研究设计新的载体策略开辟了道路,这些策略侧重于先天免疫激活作为额外的免疫接种目标,并寻求 OMV 可用于优化疫苗开发的替代形式。

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