C-Terminal Clostridium perfringens Enterotoxin-Mediated Antigen Delivery for Nasal Pneumococcal Vaccine.
C-Terminal Clostridium perfringens Enterotoxin-Mediated Antigen Delivery for Nasal Pneumococcal Vaccine.
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DOI：
10.1371/journal.pone.0126352
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kunisawa J
中科院分区：
文献类型：
--
作者：
Suzuki H;Watari A;Hashimoto E;Yonemitsu M;Kiyono H;Yagi K;Kondoh M;Kunisawa J
有效地将疫苗递送至粘膜组织（包括粘膜相关淋巴组织）对于粘膜疫苗的开发至关重要。我们先前报道了claudin-4在鼻咽相关淋巴组织（NALT）的上皮上高度表达，因此使用产气荚膜梭菌肠毒素（C-CPE）的C末端片段的claudin-4靶向有效地将融合抗原递送至NALT，从而诱导抗原特异性免疫应答。在这项研究中，我们应用C-CPE为基础的疫苗输送系统，以开发鼻肺炎球菌疫苗。我们将C-CPE与肺炎链球菌表面蛋白A（PspA）融合，PspA是诱导针对肺炎链球菌感染的保护性免疫的重要抗原（PspA-C-CPE）。PspA-C-CPE与密蛋白-4结合，从而有效地附着于NALT上皮，包括抗原取样M细胞。用PspA-C-CPE鼻免疫诱导血清和支气管肺泡灌洗液（BALF）中的PspA特异性IgG以及鼻洗液和BALF中的伊加。这些免疫反应足以保护免受肺炎球菌感染。这些结果表明，C-CPE是一个有效的疫苗输送系统的肺炎球菌感染的鼻疫苗的发展。
Efficient vaccine delivery to mucosal tissues including mucosa-associated lymphoid tissues is essential for the development of mucosal vaccine. We previously reported that claudin-4 was highly expressed on the epithelium of nasopharynx-associated lymphoid tissue (NALT) and thus claudin-4-targeting using C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE) effectively delivered fused antigen to NALT and consequently induced antigen-specific immune responses. In this study, we applied the C-CPE-based vaccine delivery system to develop a nasal pneumococcal vaccine. We fused C-CPE with pneumococcal surface protein A (PspA), an important antigen for the induction of protective immunity against Streptococcus pneumoniae infection, (PspA-C-CPE). PspA-C-CPE binds to claudin-4 and thus efficiently attaches to NALT epithelium, including antigen-sampling M cells. Nasal immunization with PspA-C-CPE induced PspA-specific IgG in the serum and bronchoalveolar lavage fluid (BALF) as well as IgA in the nasal wash and BALF. These immune responses were sufficient to protect against pneumococcal infection. These results suggest that C-CPE is an efficient vaccine delivery system for the development of nasal vaccines against pneumococcal infection.
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影响因子：
3.1
作者：
KokaiKun, JF;McClane, BA
通讯作者：
McClane, BA
影响因子：
3.1
作者：
Clark, MA;Hirst, BH;Jepson, MA
通讯作者：
Jepson, MA
影响因子：
5.5
作者：
Chung Truong Nguyen;Kim, Soo Young;Rhee, Joon Haeng
通讯作者：
Rhee, Joon Haeng
影响因子：
3.6
作者：
Kondoh, M;Masuyama, A;Watanbe, Y
通讯作者：
Watanbe, Y
新型疫苗开发策略可诱导粘膜免疫。
影响因子：
6.2
作者：
Fujkuyama Y;Tokuhara D;Kataoka K;Gilbert RS;McGhee JR;Yuki Y;Kiyono H;Fujihashi K
通讯作者：
Fujihashi K