Over-expression of superoxide dismutase obliterates the protective effect of BCG against tuberculosis by modulating innate and adaptive immune responses.

Jain, R.; Dey, B.; Khera, A.; Srivastav, P.; Gupta, U.D.; Katoch, V.M.; Ramanathan, V.D.; Tyagi, A.K.

Vaccine; 2011; 29; 8118-8125.           

Abstract: An efficient global control of tuberculosis requires development of alternative vaccination strategies that can enhance the efficacy of existing BCG vaccine. In this study, we evaluated the protective efficacy of a recombinant BCG (rBCG) vaccine over-expressing iron-cofactored superoxide dismutase (SOD-A), one of the prominent oxidative stress response proteins of Mycobacterium tuberculosis. Contrary to our expectations, over-expression of SOD-A resulted in the abrogation of BCG's ability to confer protection in guinea pig as well as in murine model. Analysis of immune responses revealed that over-expression of SOD-A by rBCG has pleiotropic effects on innate and adaptive immune responses. Macrophages infected in vitro with rBCG exhibited a marked reduction in apoptosis and microbicidal potential. In addition, rBCG vaccination of mice resulted in a reduced IFN g and increased IL10 production when compared with the BCG vaccination. Further, we show that rBCG vaccination failed to generate an effective multi-functional CD4 T cell response. Altogether, our findings suggest that over-expression of SOD-A in BCG enhances the immuno-suppressive properties of BCG, characterized by skewing of immune responses towards Th2 type, an inefficient multi-functional T cell response and reduced apoptosis and microbicidal potential of macrophages leading to abolishment of BCG's protective efficacy.

Keywords: Tuberculosis; Vaccine; Recombinant BCG; SOD; Multi-functional T cells

Back to List of publications / Home