A protein called Mycobacterial DNA-binding protein 1 (MDP1) found in Mycobacterium tuberculosis has shown to stimulate strong protective responses in individuals who are able to control tuberculosis, making it a promising candidate for a vaccine.
The current BCG vaccine for tuberculosis is given worldwide. However, with more than 10 million new tuberculosis cases reported each year, its effectiveness is considered inadequate. Consequently, efforts are being made to develop new vaccines to replace BCG. So far, no new vaccine has proven to be more effective than BCG, which is a highly successful live vaccine. Although BCG is highly effective in preventing tuberculosis in children, there is promise in creating a booster vaccine to enhance immunity in adults.
When it comes to creating vaccines for tuberculosis, scientists have examined the proteins from M. tuberculosis that activate the immune system’s defense against tuberculosis. In particular, the production of IFN-gamma by T cells is crucial for protecting against tuberculosis. Therefore, the response of IFN-gamma serves as an indicator of the effectiveness of vaccine candidate antigens. However, there is a puzzling situation where the proteins that stimulate higher production of IFN-gamma in tuberculosis patients, who have already developed the disease, are being considered as potential vaccine candidates, rather than in those who are asymptomatic carriers and prevent the onset of the disease. Additionally,Many vaccine studies do not take into account the natural three-dimensional structure of proteins and the alterations they experience after being transformed in M. tuberculosis. Furthermore, vaccine candidate molecules are often produced in basic model organisms like Escherichia coli, ignoring the specific changes that occur in molecules unique to the pathogen, such as M. tuberculosis. These modifications have been recognized as potentially important for effectively defending against real pathogen attacks. One significant protein of both BCG and M. tuberculosis is Mycobacterial DNA-binding protein 1 (MDP1).A study by Shaban et al. in 2024 found that M. tuberculosis has extensive post-translational modifications, as noted by Yoshida et al. in 2023. According to Yasuda et al. in 2024, individuals who suppress tuberculosis progression have higher IFN-gamma responses to MDP1 compared to tuberculosis patients, indicating that MDP1 could be a potential candidate for a new vaccine. Ozeki et al. conducted a study to evaluate MDP1 as a booster vaccine for tuberculosis, where they produced recombinant MDP1 and tested its ability to induce IFN-gamma using blood from BCG-vaccinated adults. Ozeki et al. also expressed MDP1 in two different hosts: M. smegmatis, a non-pathogenic, fast-growing mycobacteria. The study focused on comparing the expression of MDP1 in different bacteria, including mycobacteria and E. coli. It was found that the MDP1 expressed in M. smegmatis (mMDP1) had similar post-translational modifications to the native MDP1 in M. tuberculosis, while the one expressed in E. coli (eMDP1) did not.
In experiments with peripheral blood from adults vaccinated with BCG, it was observed that mMDP1 triggered higher levels of IFN-gamma production compared to eMDP1. This suggests that the immune system of BCG-vaccinated adults can recognize MDP1 with post-translational modifications.
these findings demonstrate the importance of post-translational modifications in the recognition of MDP1 by the immune system.demonstrated that MDP1 has a higher capacity for producing IFN-gamma compared to other vaccine antigens like Antigen 85 complex. Protein antigens used in vaccines typically require adjuvants to prevent degradation or enhance their ability to produce an immune response. Previous research has shown that MDP1, because of its ability to bind to bacterial DNA, has protected mice from M. tuberculosis infection when given alongside the vaccine. This study also showed that a combination of mMDP1 and G9.1, a new type of CpG-DNA, produced a significant amount of IFN-gamma in the blood of adults vaccinated with BCG.The findings of this research suggest that when mMDP1, which shows post-translational modifications, is combined with G9.1, it can enhance the weakening impact of BCG, showing its promise as a supplementary vaccine.
