Combined DNA vaccines formulated in DDA enhance protective immunity against tuberculosis.
This study evaluated the adjuvant Dimethyldioctyldecyl Ammonium Bromide (DDA) effect on the protective immunity induced by a combination of plasmids containing genes encoding antigens Ag85B, MPT-83, and ESAT-6 from Mycobacterium tuberculosis. The combined DNA vaccines in DDA resulted in significant increases in both specific IgG and splenic T-cell-derived Th1-type cytokine gamma interferon (IFN-gamma) production in response to the three purified antigens when compared to that of combined DNA vaccines in saline. Vaccines in DDA increased the protective efficacy of mice challenged with M. tuberculosis H37Rv as measured by reduced relative CFU counts in their lungs. Mice immunized with the combined DNA vaccines were shown to limit the growth of tubercle bacilli both in lungs and in spleens. Histopathological analyses showed that vaccinated mice had substantially improved postinfection lung pathology relative to the controls. We suggest that our combination of antigens together with DDA formulation may provide a new insight into tuberculosis prevention.
The National Laboratory of Protein Engineering and Plant Genetic Engineering, Peking University, Beijing People's Republic of China.
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D000217:Acyltransferases / Q000235:genetics / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000917:Antibody Formation; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development; D010957:Plasmids / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D017778:Vaccines, Combined / Q000276:immunology* / Q000494:pharmacology; D019444:Vaccines, DNA / Q000276:immunology* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; C094904:MPB83 protein, Mycobacterium; D008565:Membrane Proteins; D000644:Quaternary Ammonium Compounds; D017778:Vaccines, Combined; D019444:Vaccines, DNA; C015831:dimethyldioctadecylammonium; D007371:Interferon-gamma; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis