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以壳聚糖作为递送系统,用肺炎链球菌表面蛋白A(PsaA)蛋白进行黏膜免疫,可增强对急性中耳炎和肺炎链球菌侵袭性感染的防护。

Mucosal immunization with PsaA protein, using chitosan as a delivery system, increases protection against acute otitis media and invasive infection by Streptococcus pneumoniae.

作者信息

Xu J-H, Dai W-J, Chen B, Fan X-Y

机构信息

Department of Otology and Skull Base Surgery, Eye Ear Nose & Throat Hospital of Fudan University, Key Laboratory of Health Ministry for Hearing Medicine, Shanghai, China.

出版信息

Scand J Immunol. 2015 Mar;81(3):177-85. doi: 10.1111/sji.12267.

DOI:10.1111/sji.12267
PMID:25565478
Abstract

As infection with Streptococcus pneumoniae (mainly via the mucosal route) is a leading cause of acute otitis media, sinus and bacterial pneumonia, the mucosal immunity plays an important role in the prevention of pneumococcal diseases. Therefore, intranasal vaccination may be an effective immunization strategy, but requires appropriate mucosal vaccine delivery systems. In this work, chitosan was used as a mucosal delivery system to form chitosan-PsaA nanoparticles based on ionotropic gelation methods and used to immunize BALB/c mice intranasally. Compared to mice immunized with naked PsaA, levels of IFN-γ, IL-17A and IL-4 in spleen lymphocytes, the systemic (IgG in serum) and mucosal (IgA in mucosal lavage) specific antibodies were enhanced significantly in mice inoculated with chitosan-PsaA. Furthermore, increased protection against acute otitis media following middle ear challenge with pneumococcus serotype 14, and improved survival following intraperitoneal challenge with pneumococcus serotype 3 or serotype 14, was found in the mice immunized with chitosan-PsaA nanoparticles. Thus, intranasal immunization with chitosan-PsaA can successfully induce mucosal and systemic immune responses and increase protection against pneumococcal acute otitis media and invasive infections. Hence, intranasal immunization with PsaA protein, based on chitosan as a delivery system, is an efficient immunization strategy for preventing pneumococcal infections.

摘要

由于肺炎链球菌感染(主要通过黏膜途径)是急性中耳炎、鼻窦炎和细菌性肺炎的主要病因,黏膜免疫在预防肺炎球菌疾病中发挥着重要作用。因此,鼻内接种疫苗可能是一种有效的免疫策略,但需要合适的黏膜疫苗递送系统。在这项工作中,壳聚糖被用作黏膜递送系统,基于离子凝胶法形成壳聚糖 - PsaA纳米颗粒,并用于对BALB/c小鼠进行鼻内免疫。与用裸PsaA免疫的小鼠相比,接种壳聚糖 - PsaA的小鼠脾脏淋巴细胞中的IFN - γ、IL - 17A和IL - 4水平、全身(血清中的IgG)和黏膜(黏膜灌洗液中的IgA)特异性抗体均显著增强。此外,在用14型肺炎球菌进行中耳攻击后,接种壳聚糖 - PsaA纳米颗粒的小鼠对急性中耳炎的抵抗力增强,在用3型或14型肺炎球菌进行腹腔攻击后,其存活率提高。因此,用壳聚糖 - PsaA进行鼻内免疫可成功诱导黏膜和全身免疫反应,并增强对肺炎球菌性急性中耳炎和侵袭性感染的抵抗力。因此,基于壳聚糖作为递送系统的PsaA蛋白鼻内免疫是预防肺炎球菌感染的一种有效免疫策略。

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