Mucosal Adenovirus-Vectored Rv2299c Vaccine Protects Against Tuberculosis by Inducing Trained Immunity in Dendritic...

Area of Science:

• Vaccinology
• Immunology
• Infectious Diseases

Background:

• Developing effective tuberculosis (TB) vaccines beyond BCG is critical for global health, particularly for preventing adult pulmonary TB.
• Trained immunity, which broadly augments innate and adaptive responses, is underexplored in TB vaccinology.
• Dendritic cells (DCs) are key in bridging innate and adaptive immunity, making them a potential target for inducing trained immunity.

Purpose of the Study:

• To investigate Rv2299c as a standalone TB vaccine antigen.
• To evaluate if inducing trained immunity in DCs could optimize T-cell responses against TB.
• To assess the immunogenicity and protective efficacy of a novel chimpanzee adenovirus-vectored TB vaccine candidate expressing Rv2299c (rAd-Rv2299c).

Main Methods:

• Constructed a chimpanzee adenovirus-vectored TB vaccine expressing Rv2299c (rAd-Rv2299c).
• Evaluated the vaccine's immunogenicity and protective efficacy in murine models.
• Assessed DC maturation markers (MHC-II, CD86) and pro-inflammatory cytokine secretion.

Main Results:

• rAd-Rv2299c vaccination induced trained immunity in DCs, with upregulated MHC-II and CD86 expression and increased pro-inflammatory cytokine secretion.
• Immunization promoted antigen-specific polyfunctional T cells, enhancing Th1 and Th17 immune responses.
• Vaccination significantly reduced bacterial loads in the lung and spleen and attenuated pulmonary inflammation in a murine challenge model.

Conclusions:

• rAd-Rv2299c confers anti-TB protection by inducing trained immunity in DCs and promoting polyfunctional T-cell responses.
• This study provides valuable experimental evidence for developing next-generation TB vaccines.
• The findings offer conceptual insights into leveraging trained immunity for enhanced vaccine efficacy.