Mucosal Immunization with PsaA Protein, Using Chitosan as a Delivery System, Increases Protection Against Acute Otitis Media and Invasive Infection by Streptococcus pneumoniae
Mucosal Immunization with PsaA Protein, Using Chitosan as a Delivery System, Increases Protection Against Acute Otitis Media and Invasive Infection by Streptococcus pneumoniae
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DOI：
10.1111/sji.12267
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发表时间：
2015-03
影响因子：
3.7
通讯作者：
Jiang-hong Xu;Wen-jia Dai;Bing Chen;Xiao-yong Fan
中科院分区：
文献类型：
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作者：
Jiang-hong Xu;Wen-jia Dai;Bing Chen;Xiao-yong Fan
由于肺炎链球菌感染（主要通过粘膜途径）是急性中耳炎、鼻窦炎和细菌性肺炎的主要原因，因此粘膜免疫在预防肺炎球菌疾病中起着重要作用。因此，鼻内接种可能是一种有效的免疫策略，但需要适当的粘膜疫苗递送系统。在这项工作中，壳聚糖被用作粘膜递送系统，形成基于离子凝胶化方法的壳聚糖-PsaA纳米颗粒，并用于鼻内免疫BALB/c小鼠。与裸PsaA免疫组相比，壳聚糖-PsaA免疫组小鼠脾淋巴细胞中IFN-γ、IL-17 A和IL-4水平以及全身（血清中IgG）和粘膜（粘膜灌洗液中伊加）特异性抗体水平均显著升高。此外，在用壳聚糖-PsaA纳米颗粒免疫的小鼠中发现，用肺炎球菌血清型14中耳攻击后对急性中耳炎的保护增加，并且用肺炎球菌血清型3或血清型14腹膜内攻击后存活率提高。因此，用壳聚糖-PsaA鼻内免疫可以成功地诱导粘膜和全身免疫应答，并增加对肺炎球菌急性中耳炎和侵袭性感染的保护。因此，基于壳聚糖作为递送系统的PsaA蛋白的鼻内免疫是预防肺炎球菌感染的有效免疫策略。
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.