M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine
M cell-targeting strategy facilitates mucosal immune response and enhances protection against CVB3-induced viral myocarditis elicited by chitosan-DNA vaccine
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M 细胞靶向策略促进粘膜免疫反应并增强对壳聚糖 DNA 疫苗引起的 CVB3 诱导的病毒性心肌炎的保护
DOI：
10.1016/j.vaccine.2014.06.050
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发表时间：
2014-07-31
期刊：
影响因子：
5.5
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Ye, Ting;Yue, Yan;Xiong, Sidong
有效地将抗原递送到粘膜相关淋巴组织是疫苗成功诱导粘膜免疫的第一步和关键步骤。考虑到其潜在的跨细胞能力，M细胞已成为越来越有吸引力的粘膜疫苗靶点。本研究设计了一种M细胞靶向策略，通过结合产气荚膜梭菌肠毒素（CPE）的C末端30个氨基酸CPE30肽，赋予粘膜递送系统壳聚糖（CS） M细胞靶向能力，并在由CS和编码CVB3优势抗原VP1的质粒组成的柯萨奇病毒B3 （CVB3）特异性粘膜疫苗的背景下，评估其免疫增强能力。结果表明，与CS-pVP1相似，M细胞靶向CPE30-CS-pVP1疫苗呈直径约300 nm的均匀球形，zeta电位为+22 mV，能有效地保护DNA免受DNase I的酶切。小鼠每隔2周口服4剂含50 μ g pVP1的CPE30-CS-pVP1，并在末次免疫后4周再攻毒CVB3。与CS-pVP1疫苗相比，CPE30-CS-pVP1疫苗对cvb3特异性血清IgG水平和脾T细胞免疫反应无明显影响，但显著提高了特异性粪便SIgA水平，增强了粘膜T细胞免疫反应。因此，CPE30-CS-pVP1免疫组心肌炎较轻，病毒载量较低。增强的免疫原性和免疫保护作用与CPE30-CS-pVP1靶向M细胞的能力有关，从而改善了其粘膜摄取和胞吞作用。我们的研究结果表明，CPE30-CS-pVP1可能是一种针对cvb3诱导的心肌炎的新型预防性疫苗，这种M细胞靶向策略确实可以作为一种有前途的通用粘膜疫苗开发平台(C) 2014 Elsevier Ltd.。版权所有。
Efficient delivery of antigen to mucosal associated lymphoid tissue is a first and critical step for successful induction of mucosal immunity by vaccines. Considering its potential transcytotic capability, M cell has become a more and more attractive target for mucosal vaccines. In this research, we designed an M cell-targeting strategy by which mucosal delivery system chitosan (CS) was endowed with M cell-targeting ability via conjugating with a CPE30 peptide, C terminal 30 amino acids of clostridium perfringens enterotoxin (CPE), and then evaluated its immune-enhancing ability in the context of coxsackievirus B3 (CVB3)-specific mucosal vaccine consisting of CS and a plasmid encoding CVB3 predominant antigen VP1. It had shown that similar to CS-pVP1, M cell-targeting CPE30-CS-pVP1 vaccine appeared a uniform spherical shape with about 300 nm diameter and +22 mV zeta potential, and could efficiently protect DNA from DNase I digestion. Mice were orally immunized with 4 doses of CPE30-CS-pVP1 containing 50 mu g pVP1 at 2-week intervals and challenged with CVB3 4 weeks after the last immunization. Compared with CS-pVP1 vaccine, CPE30-CS-pVP1 vaccine had no obvious impact on CVB3-specific serum IgG level and splenic T cell immune responses, but significantly increased specific fecal SIgA level and augmented mucosal T cell immune responses. Consequently, much milder myocarditis and lower viral load were witnessed in CPE30-CS-pVP1 immunized group. The enhanced immunogenicity and immunoprotection were associated with the M cell-targeting ability of CPE30-CS-pVP1 which improved its mucosal uptake and transcytosis. Our findings indicated that CPE30-CS-pVP1 may represent a novel prophylactic vaccine against CVB3-induced myocarditis, and this M cell-targeting strategy indeed could be applied as a promising and universal platform for mucosal vaccine development (C) 2014 Elsevier Ltd. All rights reserved.