A novel recombinant DNA vaccine encoding Mycobacterium tuberculosis ESAT-6 and FL protects against Mycobacterium tuberculosis challenge in mice

摘要

Mycobacterium tuberculosis 6-kDa early secretory antigenic target(ESAT-6)is a dominant target antigen for cell-mediated immunity in the early phase of tuberculosis.The fms-like tyrosine kinase 3 ligand(FL)that induces potent immune response has been used as an adjuvant in vaccine development.In this study,a new recombinant plasmid(pIRES-epitope-peptides-FL)encoding three T cell epitopes of ESAT-6 and FL was constructed,and the immunogenicity of the DNA vaccine was assessed in C57BL/6 mice immunized with the plasmid DNA vaccine.Additionally,a strategy of intramuscular injection with the DNA vaccine(prime)and intranasal administration of the epitope peptides(boost)was employed to induce higher immune reaction of the mice.The results showed that mice vaccinated with the recombinant plasmid DNA vaccine and boosted with the peptides not only increased the levels of Th1 cytokines(IFN-γand IL-12),the number of IFN-γ+T cells and activities of cytotoxic T lymphocytes as well as IgG,but also enhanced protection against Mycobacterium tuberculosis challenge.In conclusion,these data indicate that the novel recombinant pIRES-epitope-peptides-FL plasmid is a useful DNA vaccine for preventing Mycobacterium tuberculosis infection.