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壳聚糖作为抗结核疫苗佐剂/递药系统合适吗?

Are chitosan natural polymers suitable as adjuvant/delivery system for anti-tuberculosis vaccines?

机构信息

Department of Microbiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.

Nanobiotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran.

出版信息

Microb Pathog. 2018 Aug;121:218-223. doi: 10.1016/j.micpath.2018.05.035. Epub 2018 May 23.

Abstract

Today, the effectiveness of the only approved tuberculosis (TB) vaccine, bacillus Calmette-Guerin (BCG), has encountered several serious problem in the control of TB infections including variable protection in adolescents and adults, the emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb) as well as HIV/AIDS co-infection. Various studies have shown that chitosan, a natural polymer, can serve as a potent carrier for the delivery of various hydrophilic molecules such as peptide, protein and drug agents due to some of its excellent characteristics including low toxicity, biodegradable and biocompatible properties and stability. Currently, these polysaccharide polymers have gained more attention as candidates for the adjuvant/delivery of anti-TB vaccines due to better cellular uptake, muco-adhesive characteristics, prolonged control release, persistent stimulation of the immune system, more efficient uptake by antigen processing cells (APCs), adjuvant/immunopotentiator function, and preventing antigen degradation in-vivo. The present study showed that the new generation of TB vaccine candidates when used in combination with chitosan and its derivatives as adjuvant or delivery system, could potently induce both protective and cell-mediated (CD4 and CD8) immune responses in animal models. In addition, they could also enhance protection against Mtb infection in TB-challenged mice and act as booster-vaccines to improve BCG-primed immunity and excellent prime-vaccines. The results of this study showed that parenteral and non-parenteral immunization of chitosan-based TB vaccines can induce appropriate immune responses; however, we suggest that based on some advantages of chitosan polymers and mucosal delivery route, non-parenteral immunization may be a better administration route for chitosan-based TB vaccines.

摘要

目前,唯一被批准用于结核病(TB)防控的疫苗卡介苗(BCG)在控制 TB 感染方面遇到了一些严重的问题,包括在青少年和成年人中的保护效果不一、结核分枝杆菌(Mtb)耐药菌株的出现以及 HIV/AIDS 合并感染。多项研究表明,壳聚糖作为一种天然聚合物,由于其具有低毒性、可生物降解和生物相容性以及稳定性等优良特性,可作为各种亲水性分子(如肽、蛋白质和药物制剂)的有效载体。目前,由于具有更好的细胞摄取能力、黏膜黏附特性、延长的控释、持续刺激免疫系统、更有效地被抗原处理细胞(APCs)摄取、佐剂/免疫增强功能以及防止抗原在体内降解等特点,这些多糖聚合物作为抗 TB 疫苗的佐剂/传递系统得到了更多的关注。本研究表明,新一代 TB 疫苗候选物与壳聚糖及其衍生物联合使用作为佐剂或传递系统,可在动物模型中强烈诱导保护性和细胞介导(CD4 和 CD8)免疫应答。此外,它们还可以增强对 TB 挑战小鼠的 Mtb 感染的保护作用,并作为增强疫苗来改善 BCG 初免免疫和优异的初免疫苗。这项研究的结果表明,壳聚糖基 TB 疫苗的肌内和非肌内免疫均可诱导适当的免疫应答;然而,我们建议,基于壳聚糖聚合物和黏膜传递途径的一些优势,非肌内免疫可能是壳聚糖基 TB 疫苗更好的给药途径。

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