Abstract
The development of a new vaccine as a substitute for Bacillus Calmette–Guerin or to improve its efficacy is one of the many World Health Organization goals to control tuberculosis. Mycobacterial vectors have been used successfully in the development of vaccines against tuberculosis. To enhance the potential utility of Mycobacterium smegmatis as a vaccine, it was transformed with a recombinant plasmid containing the partial sequences of the genes Ag85c, MPT51, and HspX (CMX) from M. tuberculosis. The newly generated recombinant strain mc2-CMX was tested in a murine model of infection. The recombinant vaccine induced specific IgG1 or IgG2a responses to CMX. CD4+ and CD8+ T cells from the lungs and spleen responded ex vivo to CMX, producing IFN-γ, IL17, TNF-α, and IL2. The vaccine thus induced a significant immune response in mice. Mice vaccinated with mc2-CMX and challenged with M. tuberculosis showed better protection than mice immunized with wild-type M. smegmatis or BCG. To increase the safety and immunogenicity of the CMX antigens, we used a recombinant strain of M. smegmatis, IKE (immune killing evasion), to express CMX. The recombinant vaccine IKE-CMX induced a better protective response than mc2-CMX. The data presented here suggest that the expression of CMX antigens improves the immune response and the protection induced in mice when M. smegmatis is used as vaccine against tuberculosis.
Highlights
Tuberculosis (TB) was the eighth most frequent cause of death worldwide in 2008 according to a World Health Organization (WHO) report, since the Millennium Development Goals and Stop TB Strategy were established by WHO, more than 51 million people have been successfully treated and cured of TB [1]
A vaccine composed of a nonpathogenic mycobacterium expressing a recombinant fusion protein composed of epitopes from M. tuberculosis (Mtb) antigens (CMX) induced a significant immune response in mice, affording them protection against Mtb challenge
Unlike pathogenic mycobacteria, these bacteria are processed upon infection and presented very rapidly by antigen-presenting cells [23]
Summary
Tuberculosis (TB) was the eighth most frequent cause of death worldwide in 2008 according to a World Health Organization (WHO) report, since the Millennium Development Goals and Stop TB Strategy were established by WHO, more than 51 million people have been successfully treated and cured of TB [1] These data are encouraging, the incidence of the disease is persistently high in several countries, explaining the continual spread of TB. Some responses in patients with extrapulmonary forms of TB are the same as those seen with the active pulmonary TB form [12,13] These features support the hypothesis that a good candidate vaccine should induce immune responses to antigens common to more than one form of TB and should include more than one protein in a single formulation. Because M. smegmatis is attenuated, grows rapidly, can express Mtb antigens, and has been shown to induce enhanced protection against TB in a murine model of infection, we used M. smegmatis expressing CMX as a recombinant vaccine
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