Vaccine · 2015
Development of a more efficient hepatitis B virus vaccine by targeting hepatitis B virus preS to dendritic cells.
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Jing Mingzhen, Wang Jun, Zhu Shengli, Ao Fang, Wang Li, Han Tao, Yue Xin, Zhu Ying, Ye Linbai, Liu Shi
Аннотация
BACKGROUND: Conventional hepatitis B virus (HBV) vaccines fail to induce protective antibody titers in 5-10% of immune-competent vaccinees. Therefore, there remains an urgent need to develop a safe and effective HBV vaccine.
METHODS: In this study, we developed an effective and economical method for producing the HBV vaccine by using the high binding capacity of biotin-streptavidin. The preS antigen of HBV was fused with the core streptavidin (cSA) moiety (preS-cSA) and highly expressed in Escherichia coli. We investigated whether the preS-cSA protein could target dendritic cells (DCs) by binding a biotinylated antibody against the DC receptor CD205 (biotin-αCD205). Moreover, we evaluated the preS-cSA/biotin-αCD205 complex as a candidate vaccine by detecting the humoral and cellular immune responses elicited by this vaccine.
RESULTS: Our data show that the preS-cSA/biotin-αCD205 complex targeted DCs and induced high anti-HBV antibody titers of IgG2a, IgG1, and IgG in vivo. Furthermore, vaccination with the preS-cSA/biotin-αCD205 complex prevented HBV infection in female mice. More interestingly, this novel vaccine exerted a therapeutic role in mice with HBV infection.
CONCLUSIONS: Taken together, our results reveal that the preS-cSA/biotin-αCD205 vaccine induces effective immunological protection against HBV, and is a promising candidate for preventing HBV infections.
METHODS: In this study, we developed an effective and economical method for producing the HBV vaccine by using the high binding capacity of biotin-streptavidin. The preS antigen of HBV was fused with the core streptavidin (cSA) moiety (preS-cSA) and highly expressed in Escherichia coli. We investigated whether the preS-cSA protein could target dendritic cells (DCs) by binding a biotinylated antibody against the DC receptor CD205 (biotin-αCD205). Moreover, we evaluated the preS-cSA/biotin-αCD205 complex as a candidate vaccine by detecting the humoral and cellular immune responses elicited by this vaccine.
RESULTS: Our data show that the preS-cSA/biotin-αCD205 complex targeted DCs and induced high anti-HBV antibody titers of IgG2a, IgG1, and IgG in vivo. Furthermore, vaccination with the preS-cSA/biotin-αCD205 complex prevented HBV infection in female mice. More interestingly, this novel vaccine exerted a therapeutic role in mice with HBV infection.
CONCLUSIONS: Taken together, our results reveal that the preS-cSA/biotin-αCD205 vaccine induces effective immunological protection against HBV, and is a promising candidate for preventing HBV infections.
Предметные рубрики MeSH
AnimalsAntibodies, MonoclonalAntigens, CDBiotinDendritic CellsFemaleHepatitis BHepatitis B AntibodiesHepatitis B Surface AntigensHepatitis B VaccinesImmunity, CellularImmunity, HumoralLectins, C-TypeMiceMice, Inbred BALB CMice, Inbred C57BLMinor Histocompatibility AntigensProtein PrecursorsReceptors, Cell SurfaceRecombinant Fusion ProteinsStreptavidin