title: Attenuated Listeria monocytogenes, a Mycobacterium tuberculosis ESAT-6 antigen expression and delivery vector for inducing an immune response.
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.
authors: Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, Jiangsu Province 225009, China. yylan@yzu.edu.cn
authors: Yuelan
authors: Y
authors: Yin
authors: Debin
authors: D
authors: Tian
authors: Yanyan
authors: Y
authors: Jia
authors: Yunfei
authors: Y
authors: Gao
authors: Hong
authors: H
authors: Fu
authors: Zhongwei
authors: Z
authors: Niu
authors: Lin
authors: L
authors: Sun
authors: Xinan
authors: X
authors: Jiao
mesh_terms: D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins; D049109:Cell Proliferation; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004337:Drug Carriers; D005822:Genetic Vectors; D006360:Heat-Shock Proteins / Q000378:metabolism; D006460:Hemolysin Proteins / Q000378:metabolism; D006461:Hemolysis; D006651:Histocytochemistry; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008089:Listeria monocytogenes / Q000235:genetics* / Q000472:pathogenicity; D008088:Listeriosis / Q000382:microbiology / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014774:Virulence
chemical_list: D000941:Antigens; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004337:Drug Carriers; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D032581:Tuberculosis Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C038705:hlyA protein, Listeria monocytogenes