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Protective immunity against group Astreptococcus infection following immunization with fibronectin-binding proteins

纤连蛋白结合蛋白免疫后对星链球菌群感染的保护性免疫力

基本信息

批准号：
18390489
负责人：
KAWABATA Shigetada
金额：
$ 10.84万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

Background. Surface-associated fibronectin (Fn) -binding proteins of group A Streptococcus pyogenes play important roles in the bacterial invasion of epithelial cells. The aim of this study was to examine the functional domain and protective antigenicity of the Fn-binding proteins FbaA and FbaB.Methods. To investigate the functional domain of FbaA or FbaB and their localization on S. pyogenes, a series of recombinant GST-truncated FbaA or FbaB proteins were employed for immunofluorescent microscopy, ligand blot, and Biacore analyses. Mice were immunized with the truncated proteins to determine the immunogenic domains that contribute to protection against S. pyogenes infection.Results. Ligand blot and Biacore analyses revealed that the FbaA fragments harboring a proline-rich repeat domain (RD), but not the N- and C-terminal regions, possessed Fn-binding activity. Immunofluorescent microscopy findings showed that the N-terminus and RD were exposed to external regions, suggesting that the RD serves as an Fn-binding element on live organisms. Specific antibodies were efficiently induced in N-terminus- and RD-immunized mice and demonstrated bactericidal activity against S. pyogenes in vitro. FbaA-immunized mice survived significantly longer as compared to the GST-immunized group following infection with M1 and M49 strains expressing FbaA. In addition, FbaB-immunized mice also survived longer than control mice after challenge with M3 strain expressing FbaB.Conclusion. The Fn-binding proteins, FbaA and FbaB, are potential vaccine candidates for S. pyogenes infection.

背景A组化脓性链球菌表面相关纤维连接蛋白（Fn）结合蛋白在细菌侵入上皮细胞中起重要作用。本研究的目的是研究Fn结合蛋白FbaA和FbaB的功能结构域和保护性抗原性。研究FbaA和FbaB的功能结构域及其在S.在化脓性链球菌中，使用一系列重组GST截短的FbaA或FbaB蛋白进行免疫荧光显微镜检查、配体印迹和Biacore分析。用截短的蛋白质免疫小鼠，以确定有助于保护免受S.化脓性链球菌感染。配体印迹和Biacore分析表明，含有富含脯氨酸的重复结构域（RD），但不是N-和C-末端区域的FbaA片段，具有Fn结合活性。免疫荧光显微镜结果表明，N-末端和RD暴露于外部区域，这表明RD作为活生物体上的Fn结合元件。在N-末端和RD-免疫的小鼠中有效地诱导特异性抗体，并表现出对S.体外培养化脓性链球菌。FbaA免疫的小鼠在感染表达FbaA的M1和M49菌株后，与GST免疫组相比存活时间显著更长。另外，FbaB免疫小鼠在用表达FbaB的M3株攻击后的存活时间也比对照组长。Fn结合蛋白FbaA和FbaB是沙门氏菌的潜在候选疫苗。化脓性感染