Abstract
One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4+ T cells. Vaccination of BALB/c mice with BM protein followed by intravenous challenge with Mycobacterium bovis BCG resulted in better levels of protection than the two leading antigens, Ag85A and PPE18. Taken together, these results indicate that BM is a protective antigen. Future studies to combine BM with other antigens and evaluate its effectiveness as a booster of BCG or as a therapeutic vaccine are warranted.
Highlights
Tuberculosis (TB) ranks alongside HIV/AIDS as a major cause of mortality by infectious diseases worldwide
The M. tb genome contains 23 esx genes, which are arranged in tandem pairs in 11 genomic loci, including five ESX loci flanked by components of type VII secretion (T7S) systems (ESX-1 to -5) (Cole et al, 1998; Abdallah et al, 2007; Bitter et al, 2009)
In mice, vaccineinduced multifunctional CD4+ T cells have been shown to correlate with protection against Leishmania major infection (Darrah et al, 2007)
Summary
Tuberculosis (TB) ranks alongside HIV/AIDS as a major cause of mortality by infectious diseases worldwide. As much as one-third of the world’s population is latently infected with M. tb and 1.5 million people died from TB in 2014. The situation has been further complicated with the advent of M. tb/HIV co-infection and the emergence of drug resistant TB. BCG exhibits highly variable efficacy against adult pulmonary TB (Brewer, 2000) and can cause disseminated BCG disease in immunocompromised individuals (WHO, 2007). In light of these situations, a more effective vaccine is urgently needed, which is essential to reduce the estimated 8–10 million new TB infections that occur annually
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