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创新型结核疫苗抗原载体系统。

Innovative antigen carrier system for the development of tuberculosis vaccines.

机构信息

Institute of Fundamental Sciences, Massey University Manawatu, Palmerston North, New Zealand.

Microbiology and Immunology Department, Otago University, Dunedin, New Zealand; and.

出版信息

FASEB J. 2019 Jun;33(6):7505-7518. doi: 10.1096/fj.201802501RR. Epub 2019 Mar 14.

DOI:10.1096/fj.201802501RR
PMID:30870010
Abstract

A major obstacle to tuberculosis (TB)-subunit-vaccine development has been the induction of inadequate levels of protective immunity due to the limited breadth of antigen in vaccine preparations. In this study, immunogenic mycobacterial fusion peptides Ag85B-TB10.4 and Ag85B-TB10.4-Rv2660c were covalently displayed on the surface of self-assembled polyester particles. This study investigated whether polyester particles displaying mycobacterial antigens could provide augmented immunogenicity (, offer an innovative vaccine formulation) when compared with free soluble antigens. Herein, polyester particle-based particulate vaccines were produced in an endotoxin-free strain and emulsified with the adjuvant dimethyl dioctadecyl ammonium bromide. C57BL/6 mice were used to study the immunogenicity of formulated particulate vaccines. The result of humoral immunity showed the antibodies only interacted with target antigens and not with PhaC and the background proteins of the production host. The analysis of T helper 1 cellular immunity indicated that a relatively strong production of cellular immunity biomarkers, IFN-γ and IL-17A cytokines, was induced by particulate vaccines when compared with the respective soluble controls. This study demonstrated that polyester particles have the potential to perform as a mycobacterial antigen-delivery agent to induce augmented antigen-specific immune responses in contrast to free soluble vaccines.-Chen, S., Sandford, S., Kirman, J. R., Rehm, B. H. A. Innovative antigen carrier system for the development of tuberculosis vaccines.

摘要

结核分枝杆菌(TB)亚单位疫苗开发的一个主要障碍是由于疫苗制剂中的抗原有限,导致诱导的保护性免疫水平不足。在这项研究中,免疫原性分枝杆菌融合肽 Ag85B-TB10.4 和 Ag85B-TB10.4-Rv2660c 被共价展示在自组装聚酯颗粒的表面。本研究旨在探讨与游离可溶性抗原相比,展示分枝杆菌抗原的聚酯颗粒是否能提供增强的免疫原性(提供创新的疫苗配方)。本文在无内毒素的 株中生产基于聚酯颗粒的颗粒状疫苗,并与佐剂二甲基十八烷基溴化铵乳化。用 C57BL/6 小鼠研究了配方颗粒疫苗的免疫原性。体液免疫的结果表明,抗体仅与靶抗原相互作用,而不与 PhaC 和生产宿主的背景蛋白相互作用。T 辅助 1 细胞免疫分析表明,与相应的可溶性对照相比,颗粒疫苗诱导产生了相对较强的细胞免疫生物标志物 IFN-γ 和 IL-17A 细胞因子。本研究表明,聚酯颗粒具有作为分枝杆菌抗原传递剂的潜力,与游离可溶性疫苗相比,可诱导增强的抗原特异性免疫反应。-Chen, S., Sandford, S., Kirman, J. R., Rehm, B. H. 用于开发结核病疫苗的创新抗原载体系统。

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