Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra
IntroductionBacillus Calmette-Guérin (BCG), the only licensed vaccine against Mycobacterium tuberculosis (Mtb) infection, has been extensively used worldwide for over 100 years, but the epidemic of tuberculosis (TB) remains a major challenge to human health and well-being. The quest for a more effe...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1430808/full |
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| author | Jiangshan Ouyang Shaohua Guo Zhiming Hu Ting Cao Jun Mou Xinxia Gu Chunxu Huang Jie Liu Jie Liu |
| author_facet | Jiangshan Ouyang Shaohua Guo Zhiming Hu Ting Cao Jun Mou Xinxia Gu Chunxu Huang Jie Liu Jie Liu |
| author_sort | Jiangshan Ouyang |
| collection | DOAJ |
| description | IntroductionBacillus Calmette-Guérin (BCG), the only licensed vaccine against Mycobacterium tuberculosis (Mtb) infection, has been extensively used worldwide for over 100 years, but the epidemic of tuberculosis (TB) remains a major challenge to human health and well-being. The quest for a more effective vaccination strategy against the Mtb infection continues. Boosting the protective immunity induced by BCG with recombinant protein is a feasible approach to improve the efficacy of BCG, due to the proven safety and effectiveness of recombinant proteins as vaccination regimes against a variety of infectious diseases. While being shown to be promising in clinical trials in preventing Mtb infection, data suggest this strategy requires further improvement.MethodsIn this study, we developed a novel fusion of proteins derived from major antigenic components of Mtb, including Ag85B, Rv2660c, and MPT70 (ARM), and assessed its antigenicity and ability to boost BCG efficacy in a murine model.ResultsThe results demonstrated that the ARM immunization induced antigen-specific T and B cell responses and reduced the Mtb H37Ra burdens in the lungs and spleen. Mice that were primed with BCG and boosted with the ARM mounted a Th1-type immune response, characterized by an increased proportion of multi-functional ARM- and Mtb lysate-specific CD4+ T cells that produced IFN-γ, TNF-α, and IL-2 compared to BCG alone, and reduced the Mtb burden without the development of severe lung pathological inflammation.DiscussionThe results of our study demonstrate that the ARM boost improves the quality of the BCG-induced immune response, increases its potency of pathogen reduction, and offers an additional option for enhancing the efficacy of BCG vaccination. |
| format | Article |
| id | doaj-art-7f05e3dde54d4dddb13df205ea074774 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-7f05e3dde54d4dddb13df205ea0747742025-08-20T02:52:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.14308081430808Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37RaJiangshan Ouyang0Shaohua Guo1Zhiming Hu2Ting Cao3Jun Mou4Xinxia Gu5Chunxu Huang6Jie Liu7Jie Liu8Laboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaLaboratory of Infectious Diseases and Vaccine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, ChinaDepartment of Healthcare Intelligence, University of North America, Fairfax, VA, United StatesIntroductionBacillus Calmette-Guérin (BCG), the only licensed vaccine against Mycobacterium tuberculosis (Mtb) infection, has been extensively used worldwide for over 100 years, but the epidemic of tuberculosis (TB) remains a major challenge to human health and well-being. The quest for a more effective vaccination strategy against the Mtb infection continues. Boosting the protective immunity induced by BCG with recombinant protein is a feasible approach to improve the efficacy of BCG, due to the proven safety and effectiveness of recombinant proteins as vaccination regimes against a variety of infectious diseases. While being shown to be promising in clinical trials in preventing Mtb infection, data suggest this strategy requires further improvement.MethodsIn this study, we developed a novel fusion of proteins derived from major antigenic components of Mtb, including Ag85B, Rv2660c, and MPT70 (ARM), and assessed its antigenicity and ability to boost BCG efficacy in a murine model.ResultsThe results demonstrated that the ARM immunization induced antigen-specific T and B cell responses and reduced the Mtb H37Ra burdens in the lungs and spleen. Mice that were primed with BCG and boosted with the ARM mounted a Th1-type immune response, characterized by an increased proportion of multi-functional ARM- and Mtb lysate-specific CD4+ T cells that produced IFN-γ, TNF-α, and IL-2 compared to BCG alone, and reduced the Mtb burden without the development of severe lung pathological inflammation.DiscussionThe results of our study demonstrate that the ARM boost improves the quality of the BCG-induced immune response, increases its potency of pathogen reduction, and offers an additional option for enhancing the efficacy of BCG vaccination.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1430808/fullmycobacterium tuberculosisBCGvaccineAg85BRv2660cMPT70 |
| spellingShingle | Jiangshan Ouyang Shaohua Guo Zhiming Hu Ting Cao Jun Mou Xinxia Gu Chunxu Huang Jie Liu Jie Liu Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra Frontiers in Immunology mycobacterium tuberculosis BCG vaccine Ag85B Rv2660c MPT70 |
| title | Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra |
| title_full | Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra |
| title_fullStr | Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra |
| title_full_unstemmed | Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra |
| title_short | Recombinant protein Ag85B-Rv2660c-MPT70 promotes quality of BCG-induced immune response against Mycobacterium tuberculosis H37Ra |
| title_sort | recombinant protein ag85b rv2660c mpt70 promotes quality of bcg induced immune response against mycobacterium tuberculosis h37ra |
| topic | mycobacterium tuberculosis BCG vaccine Ag85B Rv2660c MPT70 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1430808/full |
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