Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice
Latent tuberculosis infection (LTBI), affecting nearly one-quarter of the global population, represents a major barrier to Tuberculosis (TB) eradication and a paradigm of chronic infectious disease. Current chemotherapeutic regimens for TB, although effective, are limited by drug resistance, toxicit...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1624923/full |
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| author | Zhiming Hu Shaohua Guo Wenlong Chen Jiangshan Ouyang Chunxu Huang Ting Cao Jun Mou Xinxia Gu Jie Liu Jie Liu |
| author_facet | Zhiming Hu Shaohua Guo Wenlong Chen Jiangshan Ouyang Chunxu Huang Ting Cao Jun Mou Xinxia Gu Jie Liu Jie Liu |
| author_sort | Zhiming Hu |
| collection | DOAJ |
| description | Latent tuberculosis infection (LTBI), affecting nearly one-quarter of the global population, represents a major barrier to Tuberculosis (TB) eradication and a paradigm of chronic infectious disease. Current chemotherapeutic regimens for TB, although effective, are limited by drug resistance, toxicity, and poor adherence, underscoring the urgent need for alternative strategies. In this study, we investigated ARM—a recombinant fusion protein comprising Ag85B, Rv2660c, and MPT70—as a therapeutic vaccine in a murine model of post-exposure Mycobacterium tuberculosis (Mtb) infection. ARM immunization elicited robust CD4+ T cell responses, with a higher frequency of polyfunctional T cells producing IFN-γ, and TNF-α compared to the classical BCG vaccine. Critically, ARM also induced strong humoral immunity, marked by elevated Mtb- and ARM-specific IgG levels that enhanced FcγR-dependent phagocytosis, phagosome–lysosome fusion, and intracellular bacterial clearance. ARM-treated mice exhibited reduced pulmonary pathology, improved weight recovery, and superior control of bacterial burden. These findings demonstrate the potential of therapeutic vaccination to mobilize both cellular and antibody-mediated immunity in controlling Mtb infection and offer a broader immunological strategy for managing chronic infectious diseases. ARM represents a promising candidate for post-exposure TB vaccination, with potential to enhance bacterial clearance and reduce disease progression in high-burden populations. |
| format | Article |
| id | doaj-art-8f9035ea2b504fffbf25c1af4a642e2a |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-8f9035ea2b504fffbf25c1af4a642e2a2025-08-20T03:36:41ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-08-011610.3389/fimmu.2025.16249231624923Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure miceZhiming Hu0Shaohua Guo1Wenlong Chen2Jiangshan Ouyang3Chunxu Huang4Ting Cao5Jun Mou6Xinxia Gu7Jie Liu8Jie Liu9Center for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaCenter for Infectious Diseases and Vaccine Research, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaDepartment of Healthcare Intelligence, University of North America, Fairfax, VA, United StatesLatent tuberculosis infection (LTBI), affecting nearly one-quarter of the global population, represents a major barrier to Tuberculosis (TB) eradication and a paradigm of chronic infectious disease. Current chemotherapeutic regimens for TB, although effective, are limited by drug resistance, toxicity, and poor adherence, underscoring the urgent need for alternative strategies. In this study, we investigated ARM—a recombinant fusion protein comprising Ag85B, Rv2660c, and MPT70—as a therapeutic vaccine in a murine model of post-exposure Mycobacterium tuberculosis (Mtb) infection. ARM immunization elicited robust CD4+ T cell responses, with a higher frequency of polyfunctional T cells producing IFN-γ, and TNF-α compared to the classical BCG vaccine. Critically, ARM also induced strong humoral immunity, marked by elevated Mtb- and ARM-specific IgG levels that enhanced FcγR-dependent phagocytosis, phagosome–lysosome fusion, and intracellular bacterial clearance. ARM-treated mice exhibited reduced pulmonary pathology, improved weight recovery, and superior control of bacterial burden. These findings demonstrate the potential of therapeutic vaccination to mobilize both cellular and antibody-mediated immunity in controlling Mtb infection and offer a broader immunological strategy for managing chronic infectious diseases. ARM represents a promising candidate for post-exposure TB vaccination, with potential to enhance bacterial clearance and reduce disease progression in high-burden populations.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1624923/fullMycobacterium tuberculosistherapeutic vaccineantibody-dependent phagocytosisAg85BRv2660cMPT70 |
| spellingShingle | Zhiming Hu Shaohua Guo Wenlong Chen Jiangshan Ouyang Chunxu Huang Ting Cao Jun Mou Xinxia Gu Jie Liu Jie Liu Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice Frontiers in Immunology Mycobacterium tuberculosis therapeutic vaccine antibody-dependent phagocytosis Ag85B Rv2660c MPT70 |
| title | Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice |
| title_full | Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice |
| title_fullStr | Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice |
| title_full_unstemmed | Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice |
| title_short | Therapeutic vaccination with the Ag85B-Rv2660c-MPT70 fusion protein enhances Mycobacterium tuberculosis H37Ra clearance in post-exposure mice |
| title_sort | therapeutic vaccination with the ag85b rv2660c mpt70 fusion protein enhances mycobacterium tuberculosis h37ra clearance in post exposure mice |
| topic | Mycobacterium tuberculosis therapeutic vaccine antibody-dependent phagocytosis Ag85B Rv2660c MPT70 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1624923/full |
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