A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus.
A Multiple Antigenic Peptide Mimicking Peptidoglycan Induced T Cell Responses to Protect Mice from Systemic Infection with Staphylococcus aureus.
复制标题
DOI：
10.1371/journal.pone.0136888
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Liu BY
中科院分区：
文献类型：
--
作者：
Wang XY;Huang ZX;Chen YG;Lu X;Zhu P;Wen K;Fu N;Liu BY
由于金黄色葡萄球菌获得抗生素耐药性的巨大能力，开发用于降低其危及生命的感染风险的疫苗变得势在必行。肽聚糖（PGN）是沙门氏菌保守的主要组成部分。金黄色细胞壁。然而，由于它是一种胸腺非依赖性抗原，因此尚未用作疫苗候选物。在这项研究中，我们合成了一个多抗原肽，命名为MAP27，它包含四个拷贝的肽，模拟PGN的表位。用MAP 27免疫五次并用热灭活细菌加强一次后，抗MAP 27血清直接与S.金黄色葡萄球菌或PGN。MAP 27免疫可降低BALB/c小鼠器官中的细菌负荷，并显着延长S.金黄色葡萄球菌致死攻毒。感染后，MAP27免疫组小鼠脾脏中IFN-γ + CD3 + T细胞和IL-17 + CD4 + T细胞的百分比以及脾和肺中IFN-γ、IL-17A/F和CCL3的水平均显著升高。此外，热灭活的S.金黄色葡萄球菌与分离自MAP27免疫的小鼠的脾细胞刺激IFN-γ和IL-17A/F的产生。我们的研究结果表明，MAP27，作为一个胸腺依赖性抗原，是有效地引发T细胞介导的反应，以保护小鼠免受S。金黄色葡萄球菌感染。本研究为设计抗沙门氏菌疫苗提供了一种可能的策略。金黄色。
Due to the enormous capacity of Staphylococcus aureus to acquire antibiotic resistance, it becomes imperative to develop vaccines for decreasing the risk of its life-threatening infections. Peptidoglycan (PGN) is a conserved and major component of S. aureus cell wall. However, it has not been used as a vaccine candidate since it is a thymus-independent antigen. In this study, we synthesized a multiple antigenic peptide, named MAP27, which comprised four copies of a peptide that mimics the epitope of PGN. After immunization with MAP27 five times and boosting with heat-inactivated bacterium one time, anti-MAP27 serum bound directly to S. aureus or PGN. Immunization with MAP27 decreased the bacterial burden in organs of BALB/c mice and significantly prolonged their survival time after S. aureus lethal-challenge. The percentage of IFN-γ+CD3+ T cells and IL-17+CD4+ T cells in spleen, as well as the levels of IFN-γ, IL-17A/F and CCL3 in spleen and lung, significantly increased in the MAP27-immunized mice after infection. Moreover, in vitro incubation of heat-inactivated S. aureus with splenocytes isolated from MAP27-immunized mice stimulated the production of IFN-γ and IL-17A/F. Our findings demonstrated that MAP27, as a thymus-dependent antigen, is efficient at eliciting T cell-mediated responses to protect mice from S. aureus infection. This study sheds light on a possible strategy to design vaccines against S. aureus.