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用与M蛋白保守表位对应的合成肽进行鼻内免疫对A组链球菌黏膜定植的影响。

Influence of intranasal immunization with synthetic peptides corresponding to conserved epitopes of M protein on mucosal colonization by group A streptococci.

作者信息

Bessen D, Fischetti V A

机构信息

Rockefeller University, New York, New York 10021.

出版信息

Infect Immun. 1988 Oct;56(10):2666-72. doi: 10.1128/iai.56.10.2666-2672.1988.

Abstract

A major virulence factor of group A streptococci is M protein, a surface-exposed fibrillar molecule of which there exist more than 80 distinct serological types. Antigenic variability resides largely in the amino-terminal region of M protein, whereas the carboxy-terminal half of the molecule is highly conserved among different M serotypes. We sought to determine whether mucosal immunization with conserved epitopes of M protein influences the course of mucosal colonization by group A streptococci in a mouse model. Synthetic peptides corresponding to sequences in the conserved region of M protein were covalently linked to the mucosal adjuvant cholera toxin B subunit. Mice were immunized intranasally with the peptide-cholera toxin B subunit conjugate or with cholera toxin B subunit alone and then challenged intranasally with live streptococci. Pharyngeal colonization by streptococci was measured for up to 15 days postchallenge. Mice immunized with synthetic peptides showed a significant reduction in colonization compared with the control group. The data demonstrate that immunity evoked by conserved portions of M protein influences the outcome of group A streptococcal infection at the nasopharyngeal mucosa in a mouse model.

摘要

A群链球菌的一个主要毒力因子是M蛋白,它是一种暴露于表面的纤维状分子,存在80多种不同的血清型。抗原变异性主要存在于M蛋白的氨基末端区域,而该分子的羧基末端一半在不同的M血清型中高度保守。我们试图确定用M蛋白的保守表位进行黏膜免疫是否会在小鼠模型中影响A群链球菌的黏膜定植过程。将与M蛋白保守区域序列相对应的合成肽与黏膜佐剂霍乱毒素B亚单位共价连接。用肽 - 霍乱毒素B亚单位偶联物或仅用霍乱毒素B亚单位对小鼠进行鼻内免疫,然后用活链球菌进行鼻内攻击。在攻击后长达15天测量链球菌的咽部定植情况。与对照组相比,用合成肽免疫的小鼠定植情况显著降低。数据表明,M蛋白保守部分引发的免疫会影响小鼠模型中鼻咽黏膜处A群链球菌感染的结果。

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