Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its effic...

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Main Authors: Danang Fang, Ruihuan Wang, Xueting Fan, Machao Li, Chenyu Qian, Bin Cao, Jinjie Yu, Haican Liu, Yongliang Lou, Kanglin Wan
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Human Vaccines & Immunotherapeutics
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Online Access:https://www.tandfonline.com/doi/10.1080/21645515.2023.2299607
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author Danang Fang
Ruihuan Wang
Xueting Fan
Machao Li
Chenyu Qian
Bin Cao
Jinjie Yu
Haican Liu
Yongliang Lou
Kanglin Wan
author_facet Danang Fang
Ruihuan Wang
Xueting Fan
Machao Li
Chenyu Qian
Bin Cao
Jinjie Yu
Haican Liu
Yongliang Lou
Kanglin Wan
author_sort Danang Fang
collection DOAJ
description Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2+ and IFN-γ+IL-2+ CD4+T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro, rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.
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spelling doaj-art-4ee9fc4a68624941b96eca549443a7e92025-08-20T03:21:46ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2023.2299607Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c miceDanang Fang0Ruihuan Wang1Xueting Fan2Machao Li3Chenyu Qian4Bin Cao5Jinjie Yu6Haican Liu7Yongliang Lou8Kanglin Wan9School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaSchool of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaSchool of Public Health, University of South China, Hengyang, ChinaSchool of Public Health, University of South China, Hengyang, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaSchool of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, ChinaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, ChinaTuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) persistently kills nearly 1.5 million lives per year in the world, whereas the only licensed TB vaccine BCG exhibits unsatisfactory efficacy in adults. Taking BCG as a vehicle to express Mtb antigens is a promising way to enhance its efficacy against Mtb infection. In this study, the immune efficacy of recombination BCG (rBCG-ECD003) expressing specific antigens ESAT-6, CFP-10, and nDnaK was evaluated at different time points after immunizing BALB/c mice. The results revealed that rBCG-ECD003 induced multiple Th1 cytokine secretion including IFN-γ, TNF-α, IL-2, and IL-12 when compared to the parental BCG. Under the action of PPD or ECD003, rBCG-ECD003 immunization resulted in a significant increase in the proportion of IL-2+ and IFN-γ+IL-2+ CD4+T cells. Importantly, rBCG-ECD003 induced a stronger long-term humoral immune response without compromising the safety of the parental BCG vaccine. By means of the protective efficacy assay in vitro, rBCG-ECD003 showed a greater capacity to inhibit Mtb growth in the long term. Collectively, these features of rBCG-ECD003 indicate long-term protection and the promising effect of controlling Mtb infection.https://www.tandfonline.com/doi/10.1080/21645515.2023.2299607TuberculosisMycobacterium tuberculosisrecombinant BCG vaccinemulticomponent fusion antigencytokine
spellingShingle Danang Fang
Ruihuan Wang
Xueting Fan
Machao Li
Chenyu Qian
Bin Cao
Jinjie Yu
Haican Liu
Yongliang Lou
Kanglin Wan
Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
Human Vaccines & Immunotherapeutics
Tuberculosis
Mycobacterium tuberculosis
recombinant BCG vaccine
multicomponent fusion antigen
cytokine
title Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
title_full Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
title_fullStr Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
title_full_unstemmed Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
title_short Recombinant BCG vaccine expressing multistage antigens of Mycobacterium tuberculosis provides long-term immunity against tuberculosis in BALB/c mice
title_sort recombinant bcg vaccine expressing multistage antigens of mycobacterium tuberculosis provides long term immunity against tuberculosis in balb c mice
topic Tuberculosis
Mycobacterium tuberculosis
recombinant BCG vaccine
multicomponent fusion antigen
cytokine
url https://www.tandfonline.com/doi/10.1080/21645515.2023.2299607
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