title: A multivalent combination of experimental antituberculosis DNA vaccines based on Ag85B and regions of difference antigens.
abstract: Two candidate DNA vaccines based on the proteins CFP10 and CFP21 encoded by regions of difference (RDs) of Mycobacterium tuberculosis were evaluated individually and in multivalent combination with the immunodominant protein Ag85B for induction of protective immune responses against experimental tuberculosis. Experimental DNA vaccines induced substantial levels of cell-mediated immune responses as indicated by marked lymphocyte proliferation, significant release of the Th1 cytokines IFN-gamma and IL-12 (p40), and predominant cytotoxic T cell activity. High levels of antigen-specific IgG1 and IgG2a antibodies observed in the sera of immunized mice depicted strong humoral responses generated by DNA vaccine constructs. The multivalent combination of three DNA vaccine constructs induced maximal T cell and humoral immune responses. All the experimental vaccines imparted significant protection against challenge with M. tuberculosis H(37)Rv (in terms of colony-forming unit reduction in lungs and spleen) as compared to vector controls. The level of protection exhibited by multivalent DNA vaccine formulation was found to be equivalent to that of Mycobacterium bovis BCG observed both at 4 and 8 weeks post-challenge. These results show the protective potential of the multivalent DNA vaccine formulation used in this study.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160 012, India.
authors.forename: Ajay
authors.initials: A
authors.lastname: Grover
authors.forename: Mir Fayaz
authors.initials: MF
authors.lastname: Ahmed
authors.forename: Balwan
authors.initials: B
authors.lastname: Singh
authors.forename: Indu
authors.initials: I
authors.lastname: Verma
authors.forename: Pawan
authors.initials: P
authors.lastname: Sharma
authors.forename: G K
authors.initials: GK
authors.lastname: Khuller
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D016130:Immunophenotyping / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014376:Tuberculosis / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C117940:CFP-10 protein, Mycobacterium tuberculosis; C113719:CFP21 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA