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Protective Efficacy of Subunit Vaccine Expressing Rv0976c Against Tuberculosis

文献类型： 外文期刊

作者： Zhou, Ziwei 1 ; Chen, Dan 2 ; Chen, Fuzeng 1 ; Xu, Wenxi 3 ; Pan, Zhifen 4 ; Xiang, Zhihao 1 ; Gao, Xiaoxiao 1 ; Li, Yeyu 1 ; Zhong, Fagang 5 ; Liu, Jun 6 ; Zhang, Lu 2 ;

作者机构： 1.Fudan Univ, Inst Genet, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China

2.Fudan Univ, Sch Life Sci, Dept Microbiol, Shanghai 200433, Peoples R China

3.Princess Margaret Canc Ctr, Toronto, ON M5S 1A8, Canada

4.Jiaxing Univ, Hosp Jiaxing 1, Dept TB, Jiaxing 314001, Peoples R China

5.Xinjiang Acad Agr & Reclamat Sci, Shihezi 832000, Peoples R China

6.Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

7.Shanghai Engn Res Ctr Ind Microorganisms, Shanghai 200433, Peoples R China

关键词： tuberculosis; antigens; subunit vaccines; Rv0976c; protective efficacy

期刊名称：VACCINES （ 影响因子：3.4； 五年影响因子：3.7 ）

ISSN：

年卷期： 2025 年 13 卷 8 期

页码：

收录情况： SCI

摘要： Objectives: The construction of subunit vaccines based on antigens that can induce strong cellular immunity is a widely accepted strategy to develop new tuberculosis vaccines. This study screens immunogens with potential for subunit vaccine development from seven candidate antigens and then verifies their vaccine efficacy. Design: C57BL/6 mice were immunized subcutaneously with purified PPE19, PPE50, FadD21, Rv1505c, Rv1506c, Rv2035, and Rv0976c proteins formulated with Freund's adjuvant to evaluate both the antigen-specific Th1 cellular immune responses and IgG level. After the vaccination of mice with recombined pcDNA3.1 expressing Rv0976c, intravenous or aerosol infection with M. tb were further challenged to assess protective efficacy. Results: Purified PPE19, PPE50, FadD21, and Rv0976c proteins generated strong antigen-specific Th1 cellular immune responses in mice. Compared to Ag85A, Rv0976c also stimulated higher IgG antibody level in mice. In particular, Rv0976c stimulated high and specific IgG antibody levels in serum from TB patients. The vaccination of mice with DNA vaccines expressing Rv0976c, followed by intravenous challenge with Bacillus Calmette-Guerin (BCG) Pasteur or M. tb, resulted in significant levels of protection that are comparable to or better than that afforded by the two leading antigens, Ag85A and PPE18. Conclusions: These results indicated that Rv0976c was a better protective antigen. Future studies to combine Rv0976c with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted.

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