Heterologous Boosting With -Based Recombinant Strains in BCG-Primed Mice Improved Protection Against Pulmonary Mycobacterial Infection.

While Baccillus Calmette-Guerin (BCG) is used worldwide, tuberculosis (TB) is still a global concern due to the poor efficacy of BCG. Novel vaccine candidates are therefore urgently required. In this study, two attenuated recombinant strains, LMΔ and LIΔ were constructed by deletion of and and expression of a fusion protein consisting of T cell epitopes from four () antigens (, and ). The safety and immunogenicity of the two recombinant strains were evaluated in C57BL/6J mice. After intravenous immunization individually, both recombinant strains entered liver and spleen but eventually were eliminated from these organs after several days. Simultaneously, they induced antigen-specific cell-mediated immunity, indicating that the recombinant strains were immunogenic and safe . LMΔ immunization induced stronger cellular immune responses than LIΔ immunization, and when boosted with LIΔ, antigen-specific IFN-γ CD8 T cell responses were notably magnified. Furthermore, we evaluated the protection conferred by the vaccine candidates against mycobacterial infection via challenging the mice with 1 × 10 CFU of BCG. Especially, we tested the feasibility of application of them as heterologous BCG supplement vaccine by immunization of mice with BCG firstly, and boosted with LMΔ and LIΔ sequentially before challenging. Combination immune strategy (LMΔ prime-LIΔ boost) conferred comparable protection efficacy as BCG alone. More importantly, BCG-vaccinated mice acquired stronger resistance to Mycobacterial challenge when boosted with LMΔ and LIΔ sequentially. Our results inferred that heterologous immunization with -based recombinant strains boosted BCG-primed protection against pulmonary mycobacterial infection.