Immunogenicity of multi-epitope DNA vaccine of Mycobacterium tuberculosis and therapeutic effects of the vaccine combined with chemotherapy in a mouse model infected with multi-drug resistant Mycobacterium tuberculosis / 西安交通大学学报(医学版)

ABSTRACT

Objective To make a comparative study of the immunogenicity of multi-epitope DNA vaccine and BCG of Mycobacterium tuberculosis and therapeutic effects of the vaccines combined with chemotherapy in a mouse model infected with multi-drug resistant (MDR)Mycobacterium tuberculosis.Methods The BALB/c mice were randomly divided into Group A,Group B and Group C,which received subcutaneous immunization with PBS,BCG and multi-epitope DNA vaccine,respectively,once at weeks 1 ,3 and 5 .Specific IgG antibody,IL2 and IFN-γin mice serum were determined with ELISA after the final vaccination.At the same time,the splenic lymphocytes of mice were separated and the lymphocytes proliferation was determined by MTT method.To study the therapeutic effects of multi-epitope DNA vaccine,the mice were infected by intravenous injection in the tail vein with Mycobacterium tuberculosis clinical isolates that were resistant to isoniazid (INH)and rifampin (RFP).Four weeks later,the model mice were divided into Groups D,E and F.The mice in Group D and control group received saline injection. The mice in Group E were treated with RFP and INH.The mice in Group F were treated with multi-epitope DNA vaccine combined with INH and RFP for 10 weeks.The lungs,livers and spleens of mice were removed and weighed;the colony number of Mycobacterium tuberculosis in the lungs and spleens was counted.Results The antibody IgG,IL2 and IFN-γwere obviously higher in multi-epitope DNA vaccine group than in BCG group (P<0.05).Multi-epitope DNA vaccine combined with chemotherapy could obviously reduce the colony number of Mycobacterium tuberculosis in the lungs and spleens as well as indexes of the lungs,livers and spleens (P<0.05). Conclusion Mycobacterium tuberculosis Hsp70,Ag85A,and ESAT-6 multi-epitope DNA vaccine could induce strong specific immune response in mice that produced a high level of specific IgG antibody,IL2 and IFN-γ,specific lymphocyte proliferation,and significantly improve the efficacy of anti-tuberculosis drug resistant tuberculosis in mice.