Abstract
Although the attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921, tuberculosis (TB) control still proceeds at a slow pace. The main reason is the variable efficacy of BCG protection against TB among adults, which ranges from 0-80%. Subsequently, the mc2-CMX vaccine was developed with promising results. Nonetheless, this recombinant vaccine needs to be compared to the standard BCG vaccine. The objective of this study was to evaluate the immune response induced by mc2-CMX and compare it to the response generated by BCG. BALB/c mice were immunised with both vaccines and challenged withMycobacterium tuberculosis (Mtb). The immune and inflammatory responses were evaluated by ELISA, flow cytometry, and histopathology. Mice vaccinated with mc2-CMX and challenged with Mtb induced an increase in the IgG1 and IgG2 levels against CMX as well as recalled specific CD4+ T-cells that produced T-helper 1 cytokines in the lungs and spleen compared with BCG vaccinated and challenged mice. Both vaccines reduced the lung inflammatory pathology induced by the Mtb infection. The mc2-CMX vaccine induces a humoral and cellular response that is superior to BCG and is efficiently recalled after challenge with Mtb, although both vaccines induced similar inflammatory reductions.
Highlights
Tuberculosis (TB) has been studied since the 460 years B.C. (Benedek 2004); during the current post-genomic era, TB remains one of the most important public health problems worldwide
The humoral immune response against CMX induced by the mc2-CMX vaccine is two times higher than that induced by Bacillus Calmette-Guérin (BCG) - Because the proteins chosen to comprise the recombinant vaccine are produced by most of the mycobacteria species, it is necessary to know if there is a difference in the immunogenicity of recombinant fused protein in two different live vectors: M. smegmatis and M. bovis BCG
To assess whether Mycobacterium tuberculosis (Mtb) infection could recall the immune response induced by previous vaccination, blood samples were collected from all animals at 30 days after the infection and the levels of the anti-CMX antibodies were determined
Summary
Tuberculosis (TB) has been studied since the 460 years B.C. (Benedek 2004); during the current post-genomic era, TB remains one of the most important public health problems worldwide. Genomic studies identified deleted genes from Mycobacterium bovis responsible for the BCG attenuation process, the most important being those within the region of difference 1 (RD1) (Mahairas et al 1996, Philipp et al 1996). We developed a fusion recombinant protein, CMX, composed of the immunodominant epitopes of the Mtb proteins Ag85C, MPT-51, and HspX that was shown to induce a specific immune response in mice (de Sousa et al 2012). These studies indicated the beneficial use of the recombinant fusion CMX protein in the context of a new TB vaccine. The aim of this study was to compare the immune responses induced by the mc2-CMX and BCG vaccines
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