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用新型衍生胞外多糖佐剂配制的疫苗组合物提供了针对……的高度保护。

Vaccine Composition Formulated with a Novel -Derived Exopolysaccharides Adjuvant Provided High Protection against .

作者信息

Zhang Haochi, Pan Na, Ma Cheng, Liu Bohui, Xiu Lei, Tong He, Sheng Shouxin, Liang Yanchen, Li Haotian, Ma Fangfei, Bao Xuemei, Hu Wei, Wang Xiao

机构信息

State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

出版信息

Vaccines (Basel). 2021 Jul 12;9(7):775. doi: 10.3390/vaccines9070775.

Abstract

UNLABELLED

A vaccine that effectively targets methicillin-resistant (MRSA) is urgently needed, and has been the focus of studies by numerous research groups, but with limited success to date. Recently, our team found that exopolysaccharides derived from probiotic strain WXD030 as an adjuvant-formulated OVA could upregulate IFN-γ and IL-17 expression in CD4 T cells. In this study, we developed a vaccine (termed rMntC-EPS) composed of antigen MntC and   exopolysaccharides, which conferred high levels of protection against infection.

METHODS

Six-eight-week-old female mice were vaccinated with purified rMntC-EPS30. The immune protection function of rMntC-EPS30 was assessed by the protective effect of rMntC-EPS30 to -induced pulmonary and cutaneous infection in mice, bacterial loads and H&E in injury site, and ELISA for inflammation-related cytokines. The protective mechanism of rMntC-EPS30 was assessed by ELISA for IgG in serum, cytokines in the spleen and lungs of vaccinated mice. In addition, flow cytometry was used for analyzing cellular immune response induced by rMntC-EPS30. For confirmation of our findings, three kinds of mice were used in this study: IL-17A knockout mice, IFN-γ knockout mice and TCRγ/δ knockout mice.

RESULTS

rMntC-EPS30 conferred up to 90% protection against pulmonary infection and significantly reduced the abscess size in the cutaneous model, with clearance of the pathogen. The rMntC-EPS vaccine could induce superior humoral immunity as well as significantly increase IL-17A and IFN-γ production. In addition, we found that rMntC-EPS vaccination induced robust Th 17/γδ T 17 primary and recall responses. Interestingly, this protective effect was distinctly reduced in the IL-17A knockout mice but not in IFN-γ knockout mice. Moreover, in TCRγ/δ knockout mice, rMntC-EPS vaccination neither increased IL-17A secretion nor provided effective protection against infection.

CONCLUSIONS

These data demonstrated that the rMntC formulated with a novel -derived Exopolysaccharides adjuvant provided high protection against . The rMntC-EPS vaccine induced γδ T cells and IL-17A might play substantial roles in anti- immunity. Our findings provided direct evidence that rMntC-EPS vaccine is a promising candidate for future clinical application against -induced pulmonary and cutaneous infection.

摘要

未标记

迫切需要一种能有效靶向耐甲氧西林金黄色葡萄球菌(MRSA)的疫苗,这一直是众多研究小组的研究重点,但迄今为止成效有限。最近,我们的团队发现,源自益生菌菌株WXD030的胞外多糖作为佐剂配制的OVA可上调CD4 T细胞中IFN-γ和IL-17的表达。在本研究中,我们开发了一种由抗原MntC和胞外多糖组成的疫苗(称为rMntC-EPS),它能提供高水平的抗感染保护。

方法

用纯化的rMntC-EPS30对6-8周龄雌性小鼠进行免疫接种。通过rMntC-EPS30对小鼠肺部和皮肤感染的保护作用、损伤部位的细菌载量和苏木精-伊红染色以及炎症相关细胞因子的酶联免疫吸附测定(ELISA)来评估rMntC-EPS30的免疫保护功能。通过ELISA检测血清中的IgG、免疫接种小鼠脾脏和肺部的细胞因子来评估rMntC-EPS30的保护机制。此外,采用流式细胞术分析rMntC-EPS30诱导的细胞免疫反应。为了证实我们的发现,本研究使用了三种小鼠:IL-17A基因敲除小鼠、IFN-γ基因敲除小鼠和TCRγ/δ基因敲除小鼠。

结果

rMntC-EPS30对肺部感染提供高达90%的保护,并显著减小皮肤模型中的脓肿大小,同时清除病原体。rMntC-EPS疫苗可诱导卓越的体液免疫,并显著增加IL-17A和IFN-γ的产生。此外,我们发现rMntC-EPS免疫接种可诱导强大的Th17/γδT17初次和再次免疫反应。有趣的是,这种保护作用在IL-17A基因敲除小鼠中明显降低,但在IFN-γ基因敲除小鼠中未降低。此外,在TCRγ/δ基因敲除小鼠中,rMntC-EPS免疫接种既不增加IL-17A的分泌,也不能提供有效的抗感染保护。

结论

这些数据表明,用新型衍生胞外多糖佐剂配制的rMntC能提供高水平的抗感染保护。rMntC-EPS疫苗诱导的γδT细胞和IL-17A可能在抗免疫中发挥重要作用。我们的发现提供了直接证据,表明rMntC-EPS疫苗是未来临床应用中对抗所致肺部和皮肤感染的有前景的候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/82c0/8310297/b622ad39c5e0/vaccines-09-00775-g001.jpg

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