An Rv1471-Expressing Chimpanzee Adenovirus Vaccine Confers Protection Against Tuberculosis by Inducing Alveolar Macrophage Trained Immunity and Polyfunctional T-Cell Responses - PubMed
4 hours ago
- #trained immunity
- #tuberculosis
- #vaccine
- The study highlights the need for novel tuberculosis (TB) vaccines due to the limited protection offered by Bacille Calmette-Guérin (BCG).
- A chimpanzee adenovirus vaccine expressing the Mtb antigen Rv1471 (rAd-Rv1471) was developed to target alveolar macrophages (AMs) and induce trained immunity.
- Intranasal administration of rAd-Rv1471 in murine models reprogrammed AMs, enhancing pro-inflammatory cytokine production, MHC II and CD86 expression, and intracellular mycobacterial control.
- Transcriptomic analysis showed upregulation of key immunometabolic pathways, including Akt/mTOR/HIF-1α signaling and glycolysis.
- The vaccine also induced potent antigen-specific, polyfunctional T-cell responses in the lungs, providing dual engagement of innate and adaptive immunity.
- rAd-Rv1471 acted as an effective heterologous booster, enhancing protection in BCG-primed mice.
- The findings suggest rAd-Rv1471 as a promising dual-targeting mucosal vaccine candidate for next-generation TB vaccines.