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大肠杆菌不耐热肠毒素无毒突变体与合成肽经鼻共同免疫后对诱导麻疹病毒特异性CTL反应的佐剂作用

The adjuvant effect of a non-toxic mutant of heat-labile enterotoxin of Escherichia coli for the induction of measles virus-specific CTL responses after intranasal co-immunization with a synthetic peptide.

作者信息

Partidos C D, Pizza M, Rappuoli R, Steward M W

机构信息

Department of Clinical Sciences, London School of Hygiene and Tropical Medicine, University of London, UK.

出版信息

Immunology. 1996 Dec;89(4):483-7. doi: 10.1046/j.1365-2567.1996.d01-790.x.

Abstract

The intranasal route has been shown to be effective for immunization. However, immunization via this route may require the use of potent and safe adjuvant. The construction of non-toxic mutants of heat labile enterotoxin of Escherichia coli (LT), which is a potent mucosal adjuvant, is a major breakthrough for the development of mucosal vaccines. In this study we have assessed the ability of an LT mutant (LTK63) to act as an adjuvant following intranasal co-immunization with a peptide corresponding to a measles virus cytotoxic T lymphocyte (CTL) epitope. LTK63 was more effective at potentiating the in vivo induction of peptide-specific and measles virus-specific CTL responses than was administration of the peptide in saline. A concentration of 10 micrograms/dose of LTK63 was found to be the most effective in potentiating the in vivo priming of peptide-specific and measles virus-specific CTL responses. These findings highlight the potential of the non-toxic mutant of LT as a safe mucosal adjuvant for use in humans.

摘要

经鼻途径已被证明对免疫接种有效。然而,通过该途径进行免疫接种可能需要使用强效且安全的佐剂。构建无毒的大肠杆菌不耐热肠毒素(LT)突变体是粘膜疫苗开发的一项重大突破,LT是一种强效粘膜佐剂。在本研究中,我们评估了LT突变体(LTK63)在与对应麻疹病毒细胞毒性T淋巴细胞(CTL)表位的肽经鼻联合免疫接种后作为佐剂的能力。与在盐水中注射该肽相比,LTK63在增强体内肽特异性和麻疹病毒特异性CTL反应的诱导方面更有效。发现浓度为10微克/剂量的LTK63在增强体内肽特异性和麻疹病毒特异性CTL反应的启动方面最有效。这些发现突出了LT无毒突变体作为一种安全的粘膜佐剂用于人类的潜力。

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