Novel fusion protein REA induces robust prime protection against tuberculosis in mice
Abstract While many novel candidates for tuberculosis vaccines are presently undergoing pre-clinical or clinical trials, none of them have been able to eliminate infection entirely. In this study, we engineered a potent chimeric protein vaccine candidate, Rv2299cD2D3-ESAT-6-Ag85B (REA), which induce...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01077-1 |
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| author | Sintayehu Kebede Gurmessa Han-Gyu Choi Yong Woo Back Zongyou Jiang Thuy An Pham Seunga Choi Hwa-Jung Kim |
| author_facet | Sintayehu Kebede Gurmessa Han-Gyu Choi Yong Woo Back Zongyou Jiang Thuy An Pham Seunga Choi Hwa-Jung Kim |
| author_sort | Sintayehu Kebede Gurmessa |
| collection | DOAJ |
| description | Abstract While many novel candidates for tuberculosis vaccines are presently undergoing pre-clinical or clinical trials, none of them have been able to eliminate infection entirely. In this study, we engineered a potent chimeric protein vaccine candidate, Rv2299cD2D3-ESAT-6-Ag85B (REA), which induced Th1 and Th17 responses via dendritic cell maturation. REA-activated macrophages operated the killing mechanisms of Mycobacterium tuberculosis (MTB), such as phagosomal maturation and phagolysosome fusion, through the (PI3K)–p38 MAPK-Ca2+-NADPH oxidase pathway. Dendritic cells and macrophages activated by REA elicited synergistic anti-mycobacterial responses. Notably, REA-immunized mice suppressed MTB growth to undetectable levels at 16 weeks post-infection, which was supported by gross and pathologic findings and acid-fast staining of the lung tissues, and maintained antigen-specific multifunctional IFN-γ+IL-2+TNF-α CD4+ T and long-lasting T cells producing cytokines in the tissues. Our findings suggest that REA is an outstanding prime prophylactic vaccine candidate against tuberculosis. |
| format | Article |
| id | doaj-art-795de6c7e8b74823bb4ce83302b20a2e |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-795de6c7e8b74823bb4ce83302b20a2e2025-02-02T12:07:37ZengNature Portfolionpj Vaccines2059-01052025-01-0110111510.1038/s41541-025-01077-1Novel fusion protein REA induces robust prime protection against tuberculosis in miceSintayehu Kebede Gurmessa0Han-Gyu Choi1Yong Woo Back2Zongyou Jiang3Thuy An Pham4Seunga Choi5Hwa-Jung Kim6Department of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityDepartment of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityDepartment of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityDepartment of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityDepartment of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityR&D Center, Myco-Rapha Inc.Department of Microbiology and Medical Science, College of Medicine, Chungnam National UniversityAbstract While many novel candidates for tuberculosis vaccines are presently undergoing pre-clinical or clinical trials, none of them have been able to eliminate infection entirely. In this study, we engineered a potent chimeric protein vaccine candidate, Rv2299cD2D3-ESAT-6-Ag85B (REA), which induced Th1 and Th17 responses via dendritic cell maturation. REA-activated macrophages operated the killing mechanisms of Mycobacterium tuberculosis (MTB), such as phagosomal maturation and phagolysosome fusion, through the (PI3K)–p38 MAPK-Ca2+-NADPH oxidase pathway. Dendritic cells and macrophages activated by REA elicited synergistic anti-mycobacterial responses. Notably, REA-immunized mice suppressed MTB growth to undetectable levels at 16 weeks post-infection, which was supported by gross and pathologic findings and acid-fast staining of the lung tissues, and maintained antigen-specific multifunctional IFN-γ+IL-2+TNF-α CD4+ T and long-lasting T cells producing cytokines in the tissues. Our findings suggest that REA is an outstanding prime prophylactic vaccine candidate against tuberculosis.https://doi.org/10.1038/s41541-025-01077-1 |
| spellingShingle | Sintayehu Kebede Gurmessa Han-Gyu Choi Yong Woo Back Zongyou Jiang Thuy An Pham Seunga Choi Hwa-Jung Kim Novel fusion protein REA induces robust prime protection against tuberculosis in mice npj Vaccines |
| title | Novel fusion protein REA induces robust prime protection against tuberculosis in mice |
| title_full | Novel fusion protein REA induces robust prime protection against tuberculosis in mice |
| title_fullStr | Novel fusion protein REA induces robust prime protection against tuberculosis in mice |
| title_full_unstemmed | Novel fusion protein REA induces robust prime protection against tuberculosis in mice |
| title_short | Novel fusion protein REA induces robust prime protection against tuberculosis in mice |
| title_sort | novel fusion protein rea induces robust prime protection against tuberculosis in mice |
| url | https://doi.org/10.1038/s41541-025-01077-1 |
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