Attenuated Listeria monocytogenes, a Mycobacterium tuberculosis ESAT-6 antigen expression and delivery vector for inducing an immune response

摘要

We selectively expressed protective Mycobacterium tuberculosis antigen ESAT-6 in recombinant strains Lm(esat-6) and LmΔactA/plcB(esat-6) to evaluate the capacity of Listeria monocytogenes to deliver antigens from M. tuberculosis, and we studied the pathogenicity and immunogenicity of these strains compared with virulent parental strain yzuLm4 and attenuated strain LmΔactA/plcB. The two recombinant strains retained listeriolysin O hemolytic activity, escaped into the cytosol niche and established replication in the macrophage-like RAW264.7 cell line; however, these strains showed decreased virulence in C57BL/6 mice. Histopathology revealed no obvious pathological changes following administration of the recombinant strains to mice, indicating that they were significantly safer than parental strains. Moreover, intravenous vaccination of mice with the recombinant strains elicited specific Th1-type cellular immunity, splenocyte proliferation and effective CTL activity in vivo. Thus, attenuated L. monocytogenes strains can be used as effective vectors for delivering M. tuberculosis ESAT-6 and inducing a cellular immune response, suggesting that such vectors may be effective as novel vaccines for preventing tuberculosis.