Title: The evaluation of protective efficacy of tuberculosis DNA vaccines with different dosage and by codelivery of cytokine plasmid
Abstract: Objective:To evaluation the protective efficacy of immunization with different amount of tuberculosis DNA vaccines and codelivery of genes encoding cytokines.Methods:C57BL/6 mice were randomly divided into 14 groups, immunized with (1)the saline, (2)plasmid vector, (3)M.bovis BCG, (4)100 μg M64 and 100 μg E6 DNA, (5)50 μg M64 and 50 μg E6 DNA, (6)75 μg M64 and 25 μg E6 DNA, (7)25 μg M64 and 75 μg E6 DNA, (8)25 μg M64 and 25 μg E6 DNA, (9)100 μg M64 and 100 μg IFN-γ DNA, (10)100 μg E6 and 100 μg IFN-γ DNA, (11)100 μg M64 and 100 μg IL-12 DNA, (12)100 μg E6 and 100 μg IL-12 DNA, (13)85A DNA 100 μg, (14)85B DNA 100 μg, and then infected by intravenous injection with M.tuberculosis. Antigen-specific antibodies were determined by ELISA. The body weights of mice were weighed each week. The lungs, livers and spleens were taken and observed their pathological change, weighted and performed mycobacterial cultures.Results:The high levels of antigen-specific antibody could be detected in group 4 to 8, 13 and 14. But antigen-specific antibody did not increase in group 9 to 12. IgG2a isotype was not predominant in each group. Their ratio of antigen-specific antibody IgG2b to IgG1 obviously increased. These results suggested that they generated a Th1-biased response. The body weights in group 2, 3, 4, 8, 9, 11, 12 obviously increased at 4 weeks after infection, while in group 1, 14, 5, 6 decreased. The CFUs of lungs in group 3, 11, 9, 7 were lower. No lesions could be observed in lungs in group 10 and 13 by eyes. The different degree of hyperplasia reaction in lung tissues could be observed in group 2 to 4, 7, and 9 to 13. The hyperplasia and inflammatory infiltration reaction in lung tissues could be observed in group 1, 6, 8, 14. While only inflammatory infiltration reaction in lung tissues could be observed in group 5.Conclusion:The immunization with 100 μg of DNA vaccine could induce strong protection. The immunization with 100 μg of M64 and E6 DNA vaccines or 85A DNA vaccine could provide similar protective efficacy as live BCG. The codelivery of genes encoding cytokines IFN-γ or IL-12 could increase the effectiveness of DNA vaccines, especially IFN-γ.
Publication Year: 2006
Publication Date: 2006-01-01
Language: en
Type: article
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Cited By Count: 3
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