title: Treatment of multi-drug-resistant tuberculosis in mice with DNA vaccines alone or in combination with chemotherapeutic drugs.
abstract: The problems of tuberculosis (TB) and its drug resistances are very severe in China. New therapeutic agents or regimens to treat multi-drug-resistant tuberculosis (MDR-TB) are urgently needed. We studied the effects of Ag85A DNA vaccine alone or in combination with rifampin (RFP) or pyrazinamide (PZA) for the treatment of MDR-TB in mice. Ag85A DNA vaccine significantly increased the production of IFN-γ, but lowered the production of IL-4. Seventy female BALB/c mice infected with Mycobacterium tuberculosis clinical isolate HB361, which was resistant to RFP and isoniazid but sensitive to PZA, were treated with plasmid pVAX1, RFP, PZA, M. vaccae vaccine, Ag85A DNA, Ag85A DNA combined with RFP or PZA, respectively. Ag85A DNA vaccine alone or in combination with RFP or PZA reduced the pulmonary and splenic bacterial loads by 1.03-1.38 logs, respectively. Ag85A DNA combined with conventional chemotherapy for the treatment of MDR-TB might result in cure of MDR-TB in developing countries.
authors.affiliation: Army Tuberculosis Prevention and Control Key Laboratory, Institute of Tuberculosis Research, the 309th Hospital of Chinese PLA, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liang
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Bai
authors.forename: Q
authors.initials: Q
authors.lastname: Yu
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Li
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D000995:Antitubercular Agents / Q000627:therapeutic use*; D015169:Colony Count, Microbial; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000276:immunology / Q000302:isolation & purification; D011718:Pyrazinamide / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology / Q000627:therapeutic use*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000473:pathology; D019444:Vaccines, DNA / Q000627:therapeutic use*
chemical_list: D000942:Antigens, Bacterial; D000995:Antitubercular Agents; D032581:Tuberculosis Vaccines; D019444:Vaccines, DNA; D015847:Interleukin-4; D011718:Pyrazinamide; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis; D012293:Rifampin