Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope
Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope
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DOI：
10.1016/s0264-410x(02)00205-0
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发表时间：
2002-06-21
期刊：
影响因子：
5.5
通讯作者：
Good, MR
中科院分区：
文献类型：
--
作者：
Olive, C;Clair, T;Good, MR
A组链球菌（GAS）感染可导致风湿热（RF）和风湿性心脏病（RHD），这是一个主要的健康问题，特别是在世界各地的土著人口，特别是在澳大利亚土著人。GAS感染的主要途径是通过上呼吸道，因此，研究的主要目标是开发基于粘膜的GAS疫苗。迄今为止，大多数研究集中在GAS M蛋白上，因为对GAS的免疫是由M蛋白类型特异性调理素抗体介导的。有两个主要的障碍，以发展疫苗的变异性M蛋白和潜在的诱导自身免疫反应。因此，为了开发安全且基础广泛的疫苗，我们集中于GAS M蛋白保守的C区，并且已经鉴定了肽J8和密切相关的J8肽（J14），其可能在对GAS感染的保护性免疫中是重要的。使用粘膜动物模型系统，我们的数据显示，用粘膜佐剂、霍乱毒素B亚基（CT B）和/或白喉类毒素（dT）载体或单独的PBS鼻内免疫并用M1 GAS菌株攻击后24小时，B10.BR小鼠中出现高度的喉咙GAS定植。然而，当与CTB一起施用时，用缀合至dT或J14-dT的疫苗候选物J8鼻内免疫小鼠后，咽喉的GAS定殖显著减少。此外，与CTB和PBS免疫的对照小鼠相比，J8-dT/CTB和J14-dT/CTB免疫的小鼠具有显著更高的存活率。这些数据表明，对GAS感染的免疫可以通过用GAS M蛋白C区肽疫苗鼻内免疫来诱发，所述GAS M蛋白C区肽疫苗含有保护性B细胞表位并且缺乏T细胞自身表位。(C)2002年由Elsevier Science Ltd.出版
Infection with group A streptococci (GAS) can lead to rheumatic fever (RF) and rheumatic heart disease (RHD) which are a major health concern particularly in indigenous populations worldwide, and especially in Australian Aboriginals. A primary route of GAS infection is via the upper respiratory tract, and therefore, a major goal of research is the development of a mucosal-based GAS vaccine, The majority of the research to date has focused on the GAS M protein since immunity to GAS is mediated by M protein type-specific opsonic antibodies. There are two major impediments to the development of a vaccine-the variability in M proteins and the potential for the induction of an autoimmune response. To develop a safe and broad-based vaccine, we have therefore focused on the GAS M protein conserved C-region, and have identified peptides, J8 and the closely related J8 peptide (J14), which may be important in protective immunity to GAS infection. Using a mucosal animal model system, our data have shown a high degree of throat GAS colonisation in B10.BR mice 24 h following intranasal immunisation with the mucosal adjuvant, cholera toxin B subunit (CTB), and/or diptheria toxoid (dT) carrier, or PBS alone, and challenge with the M1 GAS strain. However, GAS colonisation of the throat was significantly reduced following intranasal immunisation of mice with the vaccine candidate J8 conjugated to dT or J14-dT when administered with CTB. Moreover, J8-dT/CTB and J14-dT/CTB-immunised mice had a significantly higher survival when compared to CTB and PBS-immunised control mice. These data indicate that immunity to GAS infection can be evoked by intranasal immunisation with a GAS M protein C-region peptide vaccine that contains a protective B cell epitope and lacks a T cell autoepitope. (C) 2002 Published by Elsevier Science Ltd.