The immunity and protective effects of antigen 85A and heat-shock protein X against progressive tuberculosis

The anti-tuberculosis vaccine, Mycobacterium bovis BCG, has been used worldwide, but its protective efficacy is variable against adult pulmonary tuberculosis. In this study, immune responses of antigen 85A (Ag85A) and heat-shock protein X (HspX) antigen of Mycobacterium tuberculosis were investigated during acute and stationary stage of infection in the murine aerosol TB challenge model and their protective effects were evaluated against progressive tuberculosis. A high level of Ag85A-specific IFN-γ production was induced from the early stage of the infection, whereas HspX-specific IFN-γ production was increased in the later stationary stage. As a subunit vaccine, Ag85A and HspX antigen vaccine induced high levels of IFN-γ, and a vaccine comprising both antigens induced the highest level of IFN-γ. At 30 days post-challenge, the Ag85A subunit vaccine was protective against M. tuberculosis challenge, but the HspX subunit vaccine was not. Interestingly, the HspX antigen vaccine induced significant protective efficacy at 90 days post-challenge. Moreover, the combined antigen vaccine induced the highest protective efficacy against M. tuberculosis challenge both at 30 days and 90 days post-challenge. These results suggest that the vaccine comprising Ag85A and HspX antigen which react in different stages of infection is highly protective against progressive tuberculosis.