Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Performance of Homologous and Heterologous Prime-Boost Immunization Regimens of Recombinant Adenovirus and Modified Vaccinia Virus Ankara Expressing an Ag85B-TB10.4 Fusion Protein against Mycobacterium tuberculosis

  • Kou, Yiming (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Wan, Mingming (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Shi, Wei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Liu, Jie (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Zhao, Zhilei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Xu, Yongqing (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Wei, Wei (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Sun, Bo (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Gao, Feng (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Cai, Linjun (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University) ;
  • Jiang, Chunlai (National Engineering Laboratory for AIDS Vaccine, School of Life Science, Jilin University)
  • Received : 2017.12.28
  • Accepted : 2018.04.03
  • Published : 2018.06.28
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Abstract

Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. In the present study, we constructed recombinant Ad and MVA expressing an Ag85B-TB10.4 fusion protein (AdH4 and MVAH4) and evaluated the impact of their different immunization regimens on the humoral and cellular immune responses. We found that the viral vector-based vaccines could generate significantly higher levels of antigen-specific antibodies, $IFN-{\gamma}$-producing splenocytes, $CD69^+CD8^+$ T cells, and $IFN-{\gamma}$ secretion when compared with bacillus Calmette-$Gu{\acute{e}}rin$ (BCG) in a mouse model. AdH4-containing immunization regimens (AdH4-AdH4, AdH4-MVAH4, and MVAH4-AdH4) induced significantly stronger antibody responses, much more $IFN-{\gamma}$-producing splenocytes and $CD69^+CD8^+$ T cells, and higher levels of $IFN-{\gamma}$ secretion when compared with the MVAH4-MVAH4 immunization regimen. The number of $IFN-{\gamma}$-producing splenocytes sensitive to $CD8^+$ T-cell restricted peptides of Ag85B (9-1p and 9-2p) and Th1-related cytokines ($IFN-{\gamma}$ and $TNF-{\alpha}$) in the AdH4-MVAH4 heterologous prime-boost regimen immunization group was significantly higher than that in the other viral vector-based vaccine- and BCG-immunized groups, respectively. These results indicate that an immunization regimen involving AdH4 may have a higher capacity to induce humoral and cellular immune responses against TB in mice than that by regimens containing BCG or MVAH4 alone, and the AdH4-MVAH4 prime-boost regimen may generate an ideal protective effect.

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References

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