B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

Shufeng Weng; Jinyi Zhang; Huixia Ma; Jingyu Zhou; Liqiu Jia; Yanmin Wan; Yanmin Wan; Peng Cui; Peng Cui; Qiaoling Ruan; Lingyun Shao; Jing Wu; Honghai Wang; Wenhong Zhang; Wenhong Zhang; Wenhong Zhang; Ying Xu; Ying Xu

doi:10.3389/fimmu.2022.1025931

Frontiers in Immunology (Dec 2022)

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

Shufeng Weng,
Jinyi Zhang,
Huixia Ma,
Jingyu Zhou,
Liqiu Jia,
Yanmin Wan,
Yanmin Wan,
Peng Cui,
Peng Cui,
Qiaoling Ruan,
Lingyun Shao,
Jing Wu,
Honghai Wang,
Wenhong Zhang,
Wenhong Zhang,
Wenhong Zhang,
Ying Xu,
Ying Xu

Affiliations

Shufeng Weng: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Jinyi Zhang: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Huixia Ma: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Jingyu Zhou: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Liqiu Jia: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Yanmin Wan: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Yanmin Wan: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Peng Cui: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Peng Cui: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Qiaoling Ruan: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Lingyun Shao: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Jing Wu: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Honghai Wang: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Wenhong Zhang: Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
Wenhong Zhang: National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
Wenhong Zhang: Key Laboratory of Medical Molecular Virology (MOE/MOH), Shanghai Medical College, Fudan University, Shanghai, China
Ying Xu: State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China
Ying Xu: Shanghai Huashen Institute of Microbes and Infections, Shanghai, China

DOI: https://doi.org/10.3389/fimmu.2022.1025931
Journal volume & issue: Vol. 13

Abstract

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Latent tuberculosis infection (LTBI) treatment is known to accelerate the decline in TB incidence, especially in high-risk populations. Mycobacterium tuberculosis (M. tb) expression profiles differ at different growth periods, and vaccines protective and therapeutic effects may increase when they include antigenic compositions from different periods. To develop a post-exposure vaccine that targets LTBI, we constructed four therapeutic DNA vaccines (A39, B37, B31, and B21) using different combinations of antigens from the proliferation phase (Ag85A, Ag85B), PE/PPE family (Rv3425), and latent phase (Rv2029c, Rv1813c, Rv1738). We compared the immunogenicity of the four DNA vaccines in C57BL/6j mice. The B21 vaccine stimulated the strongest cellular immune responses, namely Th1/Th17 and CD8+ cytotoxic T lymphocyte responses. It also induced the generation of strengthened effector memory and central memory T cells. In latently infected mice, the B21 vaccine significantly reduced bacterial loads in the spleens and lungs and decreased lung pathology. In conclusion, the B21 DNA vaccine can enhance T cell responses and control the reactivation of LTBI.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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