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利用 PLA 纳米粒递送 Vi 多糖共轭物调节免疫应答并增强伤寒沙门氏菌的清除。

Modulation of immune response and enhanced clearance of Salmonella typhi by delivery of Vi polysaccharide conjugate using PLA nanoparticles.

机构信息

Product Development Cell, National Institute of Immunology, New Delhi 110067, India; Center of Excellence in Vaccine Delivery, National Institute of Immunology, New Delhi 110067, India.

Center of Excellence in Vaccine Delivery, National Institute of Immunology, New Delhi 110067, India.

出版信息

Eur J Pharm Biopharm. 2020 Jul;152:270-281. doi: 10.1016/j.ejpb.2020.05.023. Epub 2020 May 26.

Abstract

Polysaccharide antigens do not promote antibody class switching and memory antibody response, thus require conjugation with a T cell dependent carrier protein to generate protective immune response. The intensity of immune responses varies with the carrier proteins for the same carbohydrate antigen and most of the carrier proteins do not generate strong immune responses. Vi polysaccharide and r-flagellin of Salmonella typhi were conjugated and formulated in PLA particles as nanoglycoconjugate which not only generated strong immune response but also promoted antibody class switching and elicited memory antibody response from single point immunization. Nanoglycoconjugate immunization also modulate anti-inflammatory property of Vi polysaccharide with an enhance secretion of pro-inflammatory cytokine TNF-α and IL-6. This was with concomitant decrease of IFN-γ production, antibody class switching from IgG3 to IgG2 with memory antibody generation against Vi polysaccharide. Antibody elicited by nanoglycoconjugate showed better opsonization and clearance of Salmonella typhi in THP-1 macrophages as compared to Vi-flagellin glycoconjugate and Vi TT (Typhbar®). Delivery of glycoconjugate through nanoparticles provides a platform technology for improving the immunogenicity of polysaccharide based vaccines.

摘要

多糖抗原不能促进抗体类别转换和记忆性抗体应答,因此需要与 T 细胞依赖的载体蛋白缀合,以产生保护性免疫应答。同种碳水化合物抗原的载体蛋白的免疫应答强度不同,大多数载体蛋白不能产生强烈的免疫应答。伤寒沙门氏菌的 Vi 多糖和 r-鞭毛蛋白与 PLA 颗粒缀合形成纳米糖缀合物,不仅产生了强烈的免疫应答,还促进了抗体类别转换,并在单次免疫时引发了记忆性抗体应答。纳米糖缀合物免疫还可调节 Vi 多糖的抗炎特性,增强促炎细胞因子 TNF-α 和 IL-6 的分泌。同时,IFN-γ 的产生减少,IgG3 向 IgG2 的抗体类别转换,并产生针对 Vi 多糖的记忆性抗体。与 Vi-鞭毛蛋白糖缀合物和 Vi TT(Typhbar®)相比,纳米糖缀合物诱导的抗体在 THP-1 巨噬细胞中表现出更好的调理作用和对伤寒沙门氏菌的清除作用。通过纳米颗粒递送糖缀合物为提高基于多糖的疫苗的免疫原性提供了平台技术。

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