Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.
Immunisation With Immunodominant Linear B Cell Epitopes Vaccine of Manganese Transport Protein C Confers Protection against Staphylococcus aureus Infection.
复制标题
使用免疫显性线性 B 细胞表位锰转运蛋白 C 疫苗进行免疫可预防金黄色葡萄球菌感染。
DOI：
10.1371/journal.pone.0149638
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zou QM
中科院分区：
文献类型：
--
作者：
Yang HJ;Zhang JY;Wei C;Yang LY;Zuo QF;Zhuang Y;Feng YJ;Srinivas S;Zeng H;Zou QM
金黄色葡萄球菌，特别是耐甲氧西林葡萄球菌的疫苗接种策略。金黄色葡萄球菌（MRSA）感染引起了很多研究关注。最近的努力已经选择锰转运蛋白C，或锰结合表面脂蛋白C（MntC），其是与病原体营养摄取相关的金属离子，作为S.金黄色葡萄球菌疫苗尽管对MntC的保护性体液免疫应答被充分表征，但关于详细的MntC特异性B细胞表位作图和特别是表位疫苗知之甚少，其耗时更少且更方便。在这项研究中，我们产生了重组蛋白rMntC诱导强烈的抗体反应时，用于免疫与CFA/IFA佐剂。在结果的基础上，使用一系列重叠的合成肽精细地定位MntC内的线性B细胞表位。进一步的研究表明MntC 113 -136、MntC 209 -232和MntC 263 -286可能是MntC的原始线性B细胞免疫优势表位，三维晶体结构结果表明这三个免疫优势表位均展示在MntC抗原的表面。在免疫优势肽MntC 113 -136、MntC 209 -232和MntC 263 -286的基础上，构建了S.金黄色葡萄球菌诱导偏向于TH 2的高抗体水平，并在体外针对MRSA感染提供有效的免疫保护和强的调理吞噬细胞杀伤活性。总之，该研究提供了MRSA B细胞表位疫苗设计及其用途的优化的有力证据，其基于MRSA疫苗开发中的MntC抗原。
Vaccination strategies for Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA) infections have attracted much research attention. Recent efforts have been made to select manganese transport protein C, or manganese binding surface lipoprotein C (MntC), which is a metal ion associated with pathogen nutrition uptake, as potential candidates for an S. aureus vaccine. Although protective humoral immune responses to MntC are well-characterised, much less is known about detailed MntC-specific B cell epitope mapping and particularly epitope vaccines, which are less-time consuming and more convenient. In this study, we generated a recombinant protein rMntC which induced strong antibody response when used for immunisation with CFA/IFA adjuvant. On the basis of the results, linear B cell epitopes within MntC were finely mapped using a series of overlapping synthetic peptides. Further studies indicate that MntC113-136, MntC209-232, and MntC263-286 might be the original linear B-cell immune dominant epitope of MntC, furthermore, three-dimensional (3-d) crystal structure results indicate that the three immunodominant epitopes were displayed on the surface of the MntC antigen. On the basis of immunodominant MntC113-136, MntC209-232, and MntC263-286 peptides, the epitope vaccine for S. aureus induces a high antibody level which is biased to TH2 and provides effective immune protection and strong opsonophagocytic killing activity in vitro against MRSA infection. In summary, the study provides strong proof of the optimisation of MRSA B cell epitope vaccine designs and their use, which was based on the MntC antigen in the development of an MRSA vaccine.