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鼻内给予小鼠C群脑膜炎球菌结合疫苗,同时联合使用LTK63黏膜佐剂和三甲基壳聚糖递送系统时免疫反应的调节。

Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system.

作者信息

Baudner Barbara C, Morandi Maurizio, Giuliani Marzia M, Verhoef J Coos, Junginger Hans E, Costantino Paolo, Rappuoli Rino, Del Giudice Giuseppe

机构信息

Research Center, Chiron Srl, Siena, Italy.

出版信息

J Infect Dis. 2004 Mar 1;189(5):828-32. doi: 10.1086/381708. Epub 2004 Feb 18.

Abstract

Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety.

摘要

先前的研究表明,结合疫苗抗C群脑膜炎球菌(CRM-MenC)通过鼻内(inl)与黏膜佐剂(如大肠杆菌肠毒素(LT)的突变体)以及递送系统(如壳聚糖衍生物)一起递送时,其免疫原性会增强。我们在小鼠中发现,同时使用低剂量的完全无毒LTK63突变体作为黏膜佐剂和壳聚糖的三甲基衍生物作为递送系统,能够减少诱导针对以与肌肉注射免疫相似或更高滴度鼻内递送的CRM-MenC结合疫苗产生抗体和杀菌反应所需的每种成分。这些数据可能会影响有效黏膜疫苗的设计及其安全性。

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