Publication date: Jan 31, 2025
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-Ca-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-γIL-2TNF-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.
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| Concepts | Keywords |
|---|---|
| Fast | Activated |
| Mice | Candidate |
| Mycobacterium | Clinical |
| Pathologic | Dendritic |
| Rv2299cd2d3 | Findings |
| Fusion | |
| Infection | |
| Macrophages | |
| Maturation | |
| Mtb | |
| Prime | |
| Rea | |
| Tuberculosis | |
| Vaccine | |
| Vaccines |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | IDO | protein |
| disease | MESH | tuberculosis |
| pathway | KEGG | Tuberculosis |
| disease | MESH | infection |
| pathway | REACTOME | Killing mechanisms |
| disease | MESH | infectious disease |
| pathway | REACTOME | Infectious disease |
| disease | IDO | infectious agent |
| disease | MESH | COVID 19 pandemic |
| drug | DRUGBANK | BCG vaccine |
| disease | MESH | pulmonary tuberculosis |
| disease | IDO | cell |
| drug | DRUGBANK | Cycloserine |
| disease | MESH | shock |
| disease | IDO | endotoxin |