The Initial Study On Vaccine Of Measles-Tuberculosis And The Adjuvant Effect Of CpG-ODN And PolyICLC In Tuberculosis Vaccine

[Abstract] This study is aimed to do preliminary research about the combined vaccine of measles-tuberculosis, and to observed the TLR-recognizing ligands were combined as adjuvant to enhance the immunogenicity of Mycobacterium tuberculosis fusion protein and analyze the effect of DDA on TLR-recognizing ligands. Measles attenuated vaccine and measles inactivated vaccine mixed with the fusion protein Mtb10.4-HspX (MH), and preparated the combined vaccine. MH immunized groups was used as control. Mycobacterium tuberculosis fusion protein Mtb10.4-HspX (MH) subunit vaccine was prepared by mixing CpG-ODN (CpG) and/or PolyICLC with/without DDA, and then C57BL/6mice were immunized s.c. at week1,4and7. PBS and BCG immunized groups received one time inoculation were used as controls. The serum samples of the mice were collected at6weeks after the last immunization for antibodies detection. Meanwhile, the splenic lymphocytes of mice were isolated for the detection of IFN-y production.With the stimulation of MH, HspX and PPD antigens, MH+MVi vaccine immunized mice with significantly higher production of IFN-y than MH+MV2(P<0.05),and MH+MV2vaccine immunized mice with significantly higher production of IL-4than MH+MVi (P<0.05). MH and HspX-specific IgGl, IgG2b and IgG2c induced by both of combined vaccines were significantly higher than BCG (P <0.05). In addition, IgG2c/IgGl from every combined vaccine group was higher than BCG group (P <0.05).With the stimulation of MH and HspX antigens, the mice immunized with MH+CpG+PolyICLC+DDA vaccine generated the highest level of IFN-y (P<0.05), which followed by MH+CpG+PolyICLC vaccine immunized mice with significantly higher production of IFN-y than MH+CpG and MH+PolyICLC (P<0.05). The levels of IFN-y induced by vaccines combined with DDA were respectively higher than these without DDA (P<0.05). MH and HspX-specific IgGl, IgG2b and IgG2c induced by all subunit vaccines were significantly higher than BCG (P<0.05). Notably, these antibodies were the highest in the mice immunized with MH+CpG+PolyICLC+DDA vaccine. In addition, IgG2c/IgGl from every subunit vaccine group was higher than BCG group (P<0.05).The results showed that measles attenuated-tuberculosis combined vaccine could induce a higher cellular immune responses,and CpG+PolyICLC+DDA enhanced the immunogenicity of Mycobacterium tuberculosis fusion protein. There was a synergism between CpG and PolyICLC as adjuvant. DDA was contributed to the specific cellular immune response induced by CpG and/or PolyICLC.