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一种结合五种Esx家族蛋白的融合蛋白结核疫苗的免疫原性和保护效力

Immunogenicity and Protective Efficacy of a Fusion Protein Tuberculosis Vaccine Combining Five Esx Family Proteins.

作者信息

Xiang Zhi-Hao, Sun Rui-Feng, Lin Chen, Chen Fu-Zeng, Mai Jun-Tao, Liu Yu-Xiao, Xu Zi-Yan, Zhang Lu, Liu Jun

机构信息

State Key Laboratory of Genetic Engineering, School of Life Science, Institute of Genetics, Fudan UniversityShanghai, China.

Department of Molecular Genetics, University of TorontoToronto, ON, Canada.

出版信息

Front Cell Infect Microbiol. 2017 May 31;7:226. doi: 10.3389/fcimb.2017.00226. eCollection 2017.

Abstract

One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of (). This recombinant protein, named BM, was expressed in and purified from . Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4 T cells. Vaccination of BALB/c mice with BM protein followed by intravenous challenge with BCG resulted in better levels of protection than the two leading antigens, Ag85A and PPE18. Taken together, these results indicate that BM is a protective antigen. Future studies to combine BM with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted.

摘要

开发下一代结核病疫苗的一种策略是构建基于T细胞抗原的亚单位疫苗。在本研究中,我们评估了一种融合蛋白(结合了()的EsxB、EsxD、EsxG、EsxU和EsxM)的疫苗潜力。这种重组蛋白名为BM,在()中表达并纯化。用弗氏不完全佐剂配制的纯化BM蛋白免疫C57BL/6小鼠可诱导Th1细胞因子(IFN-γ、TNF和IL-2)和多功能CD4 T细胞的产生。用BM蛋白对BALB/c小鼠进行疫苗接种,随后静脉注射卡介苗进行攻击,其保护水平优于两种主要抗原Ag85A和PPE18。综上所述,这些结果表明BM是一种保护性抗原。未来有必要开展研究,将BM与其他抗原结合,并评估其作为卡介苗增强剂或治疗性疫苗的有效性。

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