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鼻腔给予 AFCo1 佐剂与破伤风类毒素共免疫对小鼠黏膜和系统免疫应答的影响

Mucosal and systemic immune responses of mice to tetanus toxoid coadministered nasally with AFCo1.

机构信息

Immunology Department, Finlay Institute, Calle 17 esquina 198 Rpto Siboney, Havana 11600, Cuba.

出版信息

Can J Microbiol. 2011 Mar;57(3):256-61. doi: 10.1139/W11-002.

Abstract

Mucosal immune responses are an early and important line of defense against pathogens. The current understanding of the mucosal immune system allows us to consider the use of nasal immunization for induction of antigen-specific immune responses at the mucosal surface and the systemic compartment. Mucosal adjuvants are key for developing novel mucosal vaccines and represent 1 approach to improving mucosal and systemic immunity. However, few mucosal vaccine adjuvants are currently approved for human use. Neisseria meningitidis B proteoliposome-derived cochleate (AFCo1 - Adjuvant Finlay Cochleate 1) has been demonstrated to be a potent mucosal adjuvant. The present work demonstrates that intranasal immunization of 3 doses of tetanus toxoid (TT) coadministered with AFCo1 in mice promotes high systemic and mucosal responses. The anti-TT IgG serum titers and the mucosal anti-TT IgA in saliva and vaginal wash were significantly higher than TT alone. The analysis of antibody subclasses showed that intranasal administration of AFCo1 + TT induced not only IgG1 but also IgG2a anti-TT antibodies at levels comparable to those obtained with TT vaccine (vax-TET). These data support the fact that AFCo1 is a potent mucosal adjuvant in nasal immunization to a coadministered protein antigen.

摘要

黏膜免疫反应是抵御病原体的早期和重要防线。目前对黏膜免疫系统的认识使我们能够考虑使用鼻内免疫在黏膜表面和全身部位诱导抗原特异性免疫反应。黏膜佐剂是开发新型黏膜疫苗的关键,代表了提高黏膜和全身免疫的一种方法。然而,目前只有少数黏膜疫苗佐剂获得人类使用的批准。脑膜炎奈瑟菌 B 型脂蛋白体衍生的卷曲霉素(AFCo1- 福氏卷曲霉素 1 佐剂)已被证明是一种有效的黏膜佐剂。本工作表明,在小鼠中鼻内免疫接种 3 剂破伤风类毒素(TT),同时给予 AFCo1,可促进全身和黏膜的高反应。TT 单独免疫组的抗 TT 血清滴度和唾液及阴道洗液中的黏膜抗 TT IgA 明显高于 TT 单独免疫组。抗体亚类分析表明,AFCo1 鼻内给药不仅诱导了 IgG1,还诱导了 IgG2a 抗 TT 抗体,其水平可与 TT 疫苗(vax-TET)相当。这些数据支持了 AFCo1 是一种有效的黏膜佐剂,可以增强共给药蛋白抗原的鼻内免疫的事实。

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