Attenuated Listeria monocytogenes,a Mycobacterium tuberculosis ESAT-6 antigen expression and delivery vector for inducing an immune response |
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| Affiliation: | 1. Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA;2. Programs in Biochemistry, Cell, and Molecular Biology, Weill Graduate School of Medical Sciences of Cornell University, New York, NY 10065, USA;3. Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal;4. Pathogen Genomics Laboratory, Biological and Environmental Sciences and Engineering (BESE) Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Jeddah 23955-6900, Saudi Arabia;5. Global Station for Zoonosis Control, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, N20 W10 Kita-ku, Sapporo 001-0020, Japan;6. Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki 852-8523, Japan;7. Parasitology, Center for Infectious Diseases, University of Heidelberg Medical School, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany |
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| Abstract: | 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. |
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