A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice
Abstract Lung-resident memory T (TRM) cells respond rapidly and effectively to respiratory pathogen invasion, suppressing pathogen proliferation. Previously, we identified a defined TLR3 agonist called Nexavant (NVT) and developed a vaccine platform that utilizes it to induce lung TRM. In this study...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01225-7 |
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| author | Kwang Hyun Ko Seung-Hun Baek Hyun Shik Bae Young Mi Kim Sun Hwa Gu Yu Yeon Jung Eun Hye Kwak Han-Gyu Choi Hwa-Jung Kim Tae Sun Shim Dong-Ho Kim Seung Bin Cha |
| author_facet | Kwang Hyun Ko Seung-Hun Baek Hyun Shik Bae Young Mi Kim Sun Hwa Gu Yu Yeon Jung Eun Hye Kwak Han-Gyu Choi Hwa-Jung Kim Tae Sun Shim Dong-Ho Kim Seung Bin Cha |
| author_sort | Kwang Hyun Ko |
| collection | DOAJ |
| description | Abstract Lung-resident memory T (TRM) cells respond rapidly and effectively to respiratory pathogen invasion, suppressing pathogen proliferation. Previously, we identified a defined TLR3 agonist called Nexavant (NVT) and developed a vaccine platform that utilizes it to induce lung TRM. In this study, we aimed to determine whether the protective effect of TRM cells is observed in tuberculosis (TB), a chronic bacterial respiratory disease. We synthesized a peptide vaccine by elongating the CD4+ T cell epitopes from Mycobacterium tuberculosis antigens ESAT-6, CFP-10, and HspX, adjuvanted it with NVT and administered the vaccine intranasally or intramuscularly to mice. We demonstrated that intranasal administration of an NVT-formulated peptide vaccine induced the generation of CD4+ TRM cells in the lungs, and that our vaccine platform, containing a limited number of CD4 epitopes, provided protective efficacy comparable to that of the BCG vaccine, which contains multiple T cell epitopes. Furthermore, the peptides used in the vaccine were reactive in 23 out of 24 (95.8%) human PBMCs, indicating that they contain promiscuous epitopes. Our results suggest a straightforward approach to controlling pulmonary TB more effectively through the induction of lung CD4+ TRM cells, even when using the same target antigen. Additionally, this study supports a theoretical basis for developing an inhalable TB vaccine using synthetic peptides. |
| format | Article |
| id | doaj-art-6c0a4b51b7424dc488b07e8e4bc24f0b |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-6c0a4b51b7424dc488b07e8e4bc24f0b2025-08-20T03:45:44ZengNature Portfolionpj Vaccines2059-01052025-07-0110111210.1038/s41541-025-01225-7A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in miceKwang Hyun Ko0Seung-Hun Baek1Hyun Shik Bae2Young Mi Kim3Sun Hwa Gu4Yu Yeon Jung5Eun Hye Kwak6Han-Gyu Choi7Hwa-Jung Kim8Tae Sun Shim9Dong-Ho Kim10Seung Bin Cha11R&D Center, NA Vaccine InstituteInstitute for Immunology and Immunological Diseases, Yonsei University College of MedicineR&D Center, NA Vaccine InstituteInstitute for Immunology and Immunological Diseases, Yonsei University College of MedicineInstitute for Immunology and Immunological Diseases, Yonsei University College of MedicineInstitute for Immunology and Immunological Diseases, Yonsei University College of MedicineInstitute for Immunology and Immunological Diseases, Yonsei University College of MedicineDepartments of Microbiology and Translational Immunology Institute, College of Medicine, Chungnam National UniversityDepartment of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityDivision of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of MedicineR&D Center, NA Vaccine InstituteR&D Center, NA Vaccine InstituteAbstract Lung-resident memory T (TRM) cells respond rapidly and effectively to respiratory pathogen invasion, suppressing pathogen proliferation. Previously, we identified a defined TLR3 agonist called Nexavant (NVT) and developed a vaccine platform that utilizes it to induce lung TRM. In this study, we aimed to determine whether the protective effect of TRM cells is observed in tuberculosis (TB), a chronic bacterial respiratory disease. We synthesized a peptide vaccine by elongating the CD4+ T cell epitopes from Mycobacterium tuberculosis antigens ESAT-6, CFP-10, and HspX, adjuvanted it with NVT and administered the vaccine intranasally or intramuscularly to mice. We demonstrated that intranasal administration of an NVT-formulated peptide vaccine induced the generation of CD4+ TRM cells in the lungs, and that our vaccine platform, containing a limited number of CD4 epitopes, provided protective efficacy comparable to that of the BCG vaccine, which contains multiple T cell epitopes. Furthermore, the peptides used in the vaccine were reactive in 23 out of 24 (95.8%) human PBMCs, indicating that they contain promiscuous epitopes. Our results suggest a straightforward approach to controlling pulmonary TB more effectively through the induction of lung CD4+ TRM cells, even when using the same target antigen. Additionally, this study supports a theoretical basis for developing an inhalable TB vaccine using synthetic peptides.https://doi.org/10.1038/s41541-025-01225-7 |
| spellingShingle | Kwang Hyun Ko Seung-Hun Baek Hyun Shik Bae Young Mi Kim Sun Hwa Gu Yu Yeon Jung Eun Hye Kwak Han-Gyu Choi Hwa-Jung Kim Tae Sun Shim Dong-Ho Kim Seung Bin Cha A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice npj Vaccines |
| title | A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice |
| title_full | A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice |
| title_fullStr | A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice |
| title_full_unstemmed | A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice |
| title_short | A vaccine targeting lung resident-memory CD4+ T cell phenotype protects against Mycobacterium tuberculosis in mice |
| title_sort | vaccine targeting lung resident memory cd4 t cell phenotype protects against mycobacterium tuberculosis in mice |
| url | https://doi.org/10.1038/s41541-025-01225-7 |
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