Comparison of BCG prime-DNA booster and rBCG regimens for protection against tuberculosis

Developing an effective adult prophylaxis vaccine is a high priority in the global control of tuberculosis (TB), because TB remains an important public health problem and the current widely used BCG vaccine provides effective protection only for children but variable protection against adult TB. BCG priming-heterologous vaccines booster and recombinant BCG technologies have been thought as two important regimens for inducing effective protection against adult TB. Obviously, defining the protective efficacy of the two regimens would benefit more rational design of the future adult TB vaccines. In this study, a recombinant BCG strain (rBCG::685A) expressing the fusion protein of ESAT-6 and Ag85A (r685A) of Mycobacterium tuberculosis was constructed successfully and the secretion of r685A protein from rBCG strain was confirmed by western blotting with anti-ESAT-6 and anti-Ag85A polyclonal antibodies, respectively. The immune responses and protective effects in rBCG::685A vaccinated C57BL/6 mice were compared with that of our previous reported BCG prime-pcD685A booster regimen. Boosting BCG with pcD685A DNA elicited higher level of r685A protein specific IFN-γ secreted by splenocytes and a more significant increase of both TNF-α and iNOS responses in the lung, thus providing better control of bacterial growth in both lung and spleen of immunized mice challenged with virulent M. tuberculosis, compared with mice vaccinated with rBCG::685A or BCG alone. Our results have implications for development of more effective adult TB vaccines for improved control of TB.