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<p>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 <i>Mycobacterium tuberculosis</i> (MTB), such as phagosomal maturation and phagolysosome fusion, through the (PI3K)–p38 MAPK-Ca<sup>2+</sup>-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<sup>+</sup>IL-2<sup>+</sup>TNF-α CD4<sup>+</sup> 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.</p>

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Novel fusion protein REA induces robust prime protection against tuberculosis in mice

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月31日

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  • Sintayehu Kebede Gurmessa,
  • Han-Gyu Choi,
  • Yong Woo Back,
  • Zongyou Jiang,
  • Thuy An Pham,
  • Seunga Choi,
  • Hwa-Jung Kim

摘要

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.