RESUMO
Utility of Mycobacterium indicus pranii (MIP) as a multistage vaccine against mycobacterial infections demands identification of its protective antigens. We explored antigenicity and immunogenicity of a candidate protein MIP_05962 that depicts homology to HSP18 of M. leprae and antigen1 of Mycobacterium tuberculosis. This protein elicited substantial antibody response in immunized mice along with modulation of cellular immune response towards protective Th1 type. Both CD4+ and CD8+ subsets from immunized mice produced hallmark protective cytokines, IFN-γ, TNF-α and IL-2. This protein also enhanced the CD4+ effector memory that could act as first line of defence during infections. These results point to MIP_05962 as a protective antigen that contributes, in conjunction with others, to the protective immunity of this live vaccine candidate.
Assuntos
Proteínas de Bactérias/imunologia , DNA Bacteriano/imunologia , Complexo Mycobacterium avium/imunologia , Infecção por Mycobacterium avium-intracellulare/imunologia , Células Th1/imunologia , Animais , Proteínas de Bactérias/genética , Citocinas/imunologia , Citocinas/metabolismo , DNA Bacteriano/genética , Humanos , Imunidade Celular/imunologia , Imunidade Humoral/imunologia , Imunização , Camundongos , Camundongos Endogâmicos BALB C , Complexo Mycobacterium avium/genética , Infecção por Mycobacterium avium-intracellulare/microbiologia , Cultura Primária de Células , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Células Th1/metabolismo , Vacinas contra a Tuberculose/imunologiaRESUMO
The continuing incidence of leprosy infection around the world and the inability of Mycobacterium bovis bacille Calmette-Guérin (BCG) to protect certain populations clearly indicates that an improved vaccine against leprosy is needed. The immuno dominant 35 kDa protein, shared by Mycobacterium leprae and Mycobacterium avium, but not Mycobacterium tuberculosis or BCG, is recognised by >90% of leprosy patients, making it an ideal candidate antigen for a subunit vaccine. Immunization of outbred Swiss Albino mice with a DNA-35 vaccine stimulated specific T cell activation and IFN-gamma production. DNA-35 immunization induced significant levels of protection against M. leprae footpad infection, comparable to that produced by BCG. Therefore, DNA immunization with the 35 kDa antigen is effective against M. leprae infection and genetic immunization with a combination of antigens holds the potential for an improved vaccine against leprosy.
Assuntos
Antígenos de Bactérias/genética , Vacinas Bacterianas/farmacologia , DNA Bacteriano/genética , Hanseníase/imunologia , Hanseníase/prevenção & controle , Mycobacterium leprae/genética , Mycobacterium leprae/imunologia , Vacinas de DNA/farmacologia , Animais , Vacina BCG/farmacologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Sequência de Bases , Primers do DNA/genética , DNA Bacteriano/imunologia , Interferon gama/biossíntese , Hanseníase/microbiologia , Camundongos , Linfócitos T/imunologia , Vacinas de DNA/genética , Vacinas de DNA/imunologiaAssuntos
Animais , Antígenos de Bactérias/genética , Camundongos , DNA Bacteriano/genética , DNA Bacteriano/imunologia , Hanseníase/imunologia , Hanseníase/microbiologia , Hanseníase/prevenção & controle , Interferon gama/biossíntese , Linfócitos T/imunologia , Mycobacterium leprae/genética , Mycobacterium leprae/imunologia , Primers do DNA/genética , Sequência de Bases , Vacina BCG/farmacologia , Vacinas Bacterianas/farmacologia , Vacinas Bacterianas/genética , Vacinas Bacterianas/imunologia , Vacinas de DNARESUMO
Expression of the gene for a single mycobacterial antigen (Mycobacterium leprae hsp65) in adult Balb/c mice resulted in substantial cell-mediated protection against challenge with M. tuberculosis. CD4 and CD8 T cells cloned from spleens of such immunized mice passively transferred protection to non-immunized mice, and CD8 cells selectively lysed macrophages infected with M. tuberculosis. Three modes of expressing the gene have been tested: (1) expression from a retroviral vector (pZIPNeoSV) in implanted J774 tumour cells, (2) expression from the same vector via bone marrow cells transfected in vitro and used to reconstitute irradiated mice, and (3) in a preliminary experiment, from CMV immediate-early and hydroxymethylglutaryl Co-A reductase promoters injected as plasmid DNA into muscle.