Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae
Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae
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DOI：
10.1128/iai.00240-13
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发表时间：
2013-05-01
影响因子：
3.1
通讯作者：
Kiyono, Hiroshi
中科院分区：
文献类型：
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作者：
Kong, Il Gyu;Sato, Ayuko;Kiyono, Hiroshi
为了建立更安全、更有效的肺炎球菌呼吸道感染疫苗，必须整合有关肺炎球菌菌株常见抗原的现有知识以及对跨粘膜屏障递送这些抗原的系统的改进。我们开发了一种肺炎球菌疫苗，结合了肺炎球菌表面蛋白A（PspA）的优点和基于由带有阳离子胆固醇基团的支链淀粉（cCHP）组成的纳米尺寸水凝胶（纳米凝胶）的无毒鼻内疫苗递送系统。基于纳米凝胶的 PspA 鼻疫苗 (cCHP-PspA) 的功效在小鼠肺炎球菌气道感染模型中进行了测试。鼻内接种 cCHP-PspA 可提供针对肺炎链球菌 Xen10 致命攻击的保护性免疫力，减少上呼吸道和下呼吸道细菌的定植和侵袭，并诱导全身和鼻粘膜 Th17 反应、高水平的 PspA 特异性血清免疫球蛋白 G (IgG) 以及鼻和支气管 IgA 抗体反应。此外，鼻内给药后没有迹象表明纳米凝胶将 PspA 递送至嗅球或中枢神经系统。这些结果证明了基于纳米凝胶的 PspA 鼻疫苗系统作为针对肺炎球菌呼吸道感染的通用粘膜疫苗的有效性和安全性。
To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.