| Objective Due to the BCG vaccine is variably effective against tuberculosis disease, there is a great need to explore new effective vaccine.Method In our study, we constructed and designed two subunit vaccine comprising fusion protein Mtb8.4-HspX (8.4H for short) and HspX-Mtb8.4(H8.4for short)with the adjuvant DPG which was composed of DDA and poly(I:C)and gelatin. Then8.4H-DPG and H8.4-DPG were used to vaccinate mice challenged with Mtb (H37Rv), compaired with another fusion protein Mtb10.4-HspX (10.4H for short) which was reported that it could enhance BCG-primed immunity and the protective efficacy against M. tuberculosis in mice. Safety and IFN-y responses were monitored, the result showed8.4H-DPG and H8.4-DPG had different capability in immunogenic and the protective efficacy against Mtb, meanwhile gelatin contributed to an detrimental part to protective immunity. In consideration of this reason, further investigation was done,8.4H and H8.4were emulsified in DDA and vaccinated C57BL/6mice,Thl-type cytokines include IFN-y, TNF-a and IL-2were assessed. Furthermore, the human T-cell responses to8.4H and H8.4were evaluated. At the same time, the relationship between inoculation dosage and immunogenic efficacy was explored from Thl responses to Th2responses.Results In conclusion,8.4H and H8.4could generate strong antigen-specific humoral and cell-mediated immunity, and led to significantly different level of Thl immune response in C57BL/6mice. The result also showed antigen dose can greatly influence the induction of Th1-type cytokines, and lower dose were more likely to promote T-cell proliferation and produce long-lived memory cells than effector cells.Conclusion Safety and immunogenicity of subunit vaccine is related to protein structure and vaccination dosage, therefore the optimal vaccination dose and vaccine construction was crucial for evaluating new vaccines. |
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