Modified BCG targeting DEC-205 receptor boosts dendritic cell uptake and sustained lung protection in mice

Researchers at the Centenary Institute and University of Sydney engineered BCG to display a single-chain antibody fragment that binds DEC-205 on dendritic cells. In C57BL/6 mice, the modified strain was internalized more efficiently, driving higher frequencies of polyfunctional CD4+ T cells that produced IFN-γ, TNF, and IL-2 simultaneously. After aerosol challenge, lung bacterial loads remained significantly lower at 24 weeks post-vaccination than in animals given parental BCG.

Standard BCG efficacy wanes in adults partly because it elicits limited dendritic-cell activation and short-lived T-cell memory. By redirecting uptake through DEC-205, the modified vaccine bypassed this bottleneck without increasing reactogenicity in the short-term mouse model. The approach aligns with earlier DEC-205-targeting strategies tested for HIV and malaria vaccines, suggesting a reusable platform.

Translation to humans remains uncertain. Mouse TB models do not fully recapitulate human latency or granuloma dynamics, and no data yet exist on safety, immunogenicity, or efficacy in primates or people. Next steps require GLP toxicology, dose-finding in non-human primates, and eventual phase 1 trials in BCG-naïve adults.