DNA-Launched Alphavirus Replicons Encoding a Fusion of Mycobacterial Antigens Acr and Ag85B Are Immunogenic and Protective in a Murine Model of TB Infection.

There is an urgent need for effective prophylactic measures against Mycobacterium tuberculosis (Mtb) infection, particularly given the highly variable efficacy of Bacille Calmette-Guerin (BCG), the only licensed vaccine against tuberculosis (TB). Most studies indicate that cell-mediated immune responses involving both CD4+ and CD8+ T cells are necessary for effective immunity against Mtb. Genetic vaccination induces humoral and cellular immune responses, including CD4+ and CD8+ T-cell responses, against a variety of bacterial, viral, parasitic and tumor antigens, and this strategy may therefore hold promise for the development of more effective TB vaccines.

Prime-boost approaches to tuberculosis vaccine development.

Four individuals die from active TB disease each minute, while at least 2 billion are latently infected and at risk for disease reactivation. BCG, the only licensed TB vaccine, is effective in preventing childhood forms of TB; however its poor efficacy in adults, emerging drug-resistant TB strains and tedious chemotherapy regimes, warrant the development of novel prophylactic measures. Designing safe and effective vaccines against TB will require novel approaches on several levels, including the administration of rationally selected mycobacterial antigens in efficient delivery vehicles via optimal immunization routes.