Live Bacteria Therapy for TB Immunotherapy Using Ag85AB as Vector and Targeted Liposome Delivery system

This project proposes a novel synthetic biology-based therapeutic strategy for tuberculosis (TB), addressing the critical limitations of current treatment approaches including multidrug resistance (MDR/RR-TB), prolonged treatment durations, and therapy-induced dysbiosis. With TB affecting approximately 22% of the global population and over 10.6 million new cases reported in 2021 (WHO Global Tuberculosis Report 2022), there is an urgent need for innovative treatment alternatives. The proposed intervention combines live bacteria therapy with a targeted liposome delivery system, using Lactobacillus as a vector engineered to carry the Ag85A/B plasmid (pVAX1, 3.0 kb). The Ag85A and Ag85B antigens are well-characterized immunogenic proteins of Mycobacterium tuberculosis known to stimulate robust cellular immune responses. Once delivered via inhalation through targeted liposomes, the live bacteria are engulfed by macrophages, triggering antigen presentation and activating both CD4+ and CD8+ T-cell mediated immunity. Key advantages of this approach include dual utility as both a vaccine and immunotherapy agent, targeted pulmonary delivery, long-lasting immune protection through bacterial persistence, and reduced need for repeated dosing. Biosafety considerations and limitations — particularly for immunocompromised populations such as HIV-positive patients — are also discussed, along with the variability of host immune responses as a challenge to consistent therapeutic outcomes. This work was conducted as part of the Synthetic Biology for All (SynBio for All) program.