Adjunct immunotherapy with Ag85 complex proteins based subunit vaccine in a murine model of Mycobacterium tuberculosis infection.
This study was designed to evaluate the immunotherapeutic potential of Mycobacterium tuberculosis Ag85AB emulsified with unmethylated CpG motif-containing oligonucleotide (CpG-ODN) and dimethyldioctadecylammonium bromide (DDA) adjuvants (Ag85AB-CpG-DDA) in conjunction with antituberculous drugs. Ag85 complex proteins of M. tuberculosis purified from total culture filtrate and purified proteins were emulsified with CpG-ODN and DDA adjuvants. Mice were infected with M. tuberculosis H37 Rv and left for 30 days to establish infection. These mice were named 'tuberculous mice'. Tuberculous mice were treated with Ag85AB-CpG-DDA alone or in conjunction with antituberculous drugs. Treatment of tuberculous mice with Ag85AB-CpG-DDA in conjunction with antituberculous drugs reduced significant bacilli burden in lung and spleen. Moreover, treatment of tuberculous mice with Ag85AB-CpG-DDA induced higher production of type-I cytokines, generated more CD44-positive T cells and suppresses secretion of IL-4 as compared with untreated animals. In conclusion, this study shows that Ag85AB-CpG-DDA formulation may act as a potential future therapeutic regimen in conjunction with antituberculous drugs.
Giri
Pramod K
PK
University of Notre Dame, IN, USA.
Verma
Indu
I
Khuller
Gopal K
GK
D000217:Acyltransferases / Q000008:administration & dosage* / Q000737:chemistry; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000737:chemistry; D058491:Bacterial Load / Q000187:drug effects / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000737:chemistry; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000737:chemistry; D002478:Cells, Cultured; D006801:Humans; D007167:Immunotherapy; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C408982:CPG-oligonucleotide; D009838:Oligodeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; D015847:Interleukin-4; C015831:dimethyldioctadecylammonium; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis