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多组分金纳米糖缀合物作为一种针对……的高免疫原性和保护性平台

Multicomponent gold nano-glycoconjugate as a highly immunogenic and protective platform against .

作者信息

Tapia Daniel, Sanchez-Villamil Javier I, Torres Alfredo G

机构信息

Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77550 USA.

Department of Pathology, University of Texas Medical Branch, Galveston, TX 77550 USA.

出版信息

NPJ Vaccines. 2020 Sep 10;5:82. doi: 10.1038/s41541-020-00229-9. eCollection 2020.

Abstract

() is a facultative intracellular pathogen and the etiological agent of glanders, a highly infectious zoonotic disease occurring in equines and humans. The intrinsic resistance to antibiotics, lack of specific therapy, high mortality, and history as a biothreat agent, prompt the need of a safe and effective vaccine. However, the limited knowledge of protective -specific antigens has hampered the development of a vaccine. Further, the use of antigen-delivery systems that enhance antigen immunogenicity and elicit robust antigen-specific immune responses has been limited and could improve vaccines against . Nanovaccines, in particular gold nanoparticles (AuNPs), have been investigated as a strategy to broaden the repertoire of vaccine-mediated immunity and as a tool to produce multivalent vaccines. To synthesize a nano-glycoconjugate vaccine, six predicted highly immunogenic antigens identified by a genome-wide bio- and immuno-informatic analysis were purified and coupled to AuNPs along with lipopolysaccharide (LPS) from . Mice immunized intranasally with individual AuNP-protein-LPS conjugates, showed variable degrees of protection against intranasal infection, while an optimized combination formulation (containing protein antigens OmpW, OpcP, and Hemagglutinin, along with LPS) showed complete protection against lethality in a mouse model of inhalational glanders. Animals immunized with different nano-glycoconjugates showed robust antigen-specific antibody responses. Moreover, serum from animals immunized with the optimized nano-glycoconjugate formulation showed sustained antibody responses with increased serum-mediated inhibition of adherence and opsonophagocytic activity in vitro. This study provides the basis for the rational design and construction of a multicomponent vaccine platform against .

摘要

()是一种兼性细胞内病原体,也是鼻疽的病原体,鼻疽是一种在马和人类中发生的高度传染性人畜共患病。其对抗生素的固有抗性、缺乏特异性治疗方法、高死亡率以及作为生物威胁剂的历史,促使人们需要一种安全有效的疫苗。然而,对保护性特异性抗原的了解有限阻碍了疫苗的开发。此外,增强抗原免疫原性并引发强大的抗原特异性免疫反应的抗原递送系统的使用一直有限,而这可能会改进针对(该病原体)的疫苗。纳米疫苗,特别是金纳米颗粒(AuNPs),已被研究作为一种扩大疫苗介导免疫范围的策略以及生产多价疫苗的工具。为了合成一种纳米糖缀合物疫苗,通过全基因组生物和免疫信息分析鉴定出的六种预测的高免疫原性抗原被纯化,并与来自(该病原体)的脂多糖(LPS)一起偶联到金纳米颗粒上。用单个金纳米颗粒 - 蛋白质 - LPS缀合物经鼻内免疫的小鼠,对鼻内(该病原体)感染表现出不同程度的保护作用,而一种优化的组合制剂(包含蛋白质抗原OmpW、OpcP和血凝素以及LPS)在吸入性鼻疽小鼠模型中显示出对致死性的完全保护。用不同纳米糖缀合物免疫的动物表现出强大的抗原特异性抗体反应。此外,用优化的纳米糖缀合物制剂免疫的动物血清显示出持续的抗体反应,体外血清介导的粘附抑制和调理吞噬活性增加。本研究为合理设计和构建针对(该病原体)的多组分疫苗平台提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e33/7483444/1886232aea2c/41541_2020_229_Fig1_HTML.jpg

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