An autophagosome-based therapeutic vaccine for HBV infection: a preclinical evaluation.
An autophagosome-based therapeutic vaccine for HBV infection: a preclinical evaluation.
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基于自噬体的 HBV 感染治疗疫苗：临床前评估
DOI：
10.1186/s12967-014-0361-4
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发表时间：
2014-12-20
影响因子：
7.4
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Xue M;Fan F;Ding L;Liu J;Su S;Yin P;Cao M;Zhao W;Hu HM;Wang L
全球超过2.4亿慢性HBV携带者迫切需要有效的治疗性HBV疫苗。最近，我们证明自噬体是有效的抗原载体，能够交叉启动强大的t细胞反应并介导多种肿瘤的消退。在这里，我们测试了来自HBV表达细胞的自噬体是否也可以作为治疗性疫苗。方法从表达HBV的肝癌细胞中制备基于自噬体的HBV疫苗，并在模拟人急性和慢性HBV感染的小鼠模型中检测其诱导多价抗HBV t细胞反应的能力和治疗效果。结果与基于重组HBsAg的疫苗相比，基于自噬体的HBV疫苗交叉引发多特异性抗HBV t细胞反应，并显著降低了急性和慢性小鼠模型肝脏中的HBV复制和HBcAg表达。在慢性小鼠模型中，该HBV疫苗的治疗效果依赖于抗HBV CD8+效应T细胞，并与HBsAg和HBcAg特异性IFN-γ产生T细胞增加相关。结论基于自噬体的HBV疫苗能有效抑制HBV复制，清除HBV感染的肝细胞，打破小鼠HBV耐受。讨论了基于自噬体的HBV疫苗的潜在临床应用。
BackgroundFor more than 240 million chronic HBV carriers worldwide, effective therapeutic HBV vaccines are urgently needed. Recently, we demonstrated that autophagosomes were efficient antigens carriers and capable to cross-prime robust T-cell responses and mediate regression of multiple established tumors. Here we tested whether autophagosomes derived from HBV expressing cells could also function as a therapeutic vaccine.MethodsWe generated an autophagosome-based HBV vaccine from HBV-expressing hepatoma cells and examined its ability to induce polyvalent anti-HBV T-cell responses and therapeutic efficacy in mouse models that mimic acute and chronic HBV infection in human.ResultsWhen compared to the vaccine based on recombinant HBsAg, autophagosome-based HBV vaccine cross-primed multi-specific anti-HBV T-cell responses and significantly reduced HBV replication and HBcAg expression in livers of both acute and chronic mouse models. Therapeutic effect of this HBV vaccine depended on anti-HBV CD8+effector T cells and associated with increased HBsAg and HBcAg specific IFN-γ producing T cells in the chronic mouse model.ConclusionsThese results indicated that autophagosome-based HBV vaccine could effectively suppress the HBV replication, clear the HBV infected hepatocytes, and break the HBV tolerance in mouse model. The potential clinical application of autophagosome-based HBV vaccine is discussed.
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影响因子：
38.3
作者：
通讯作者：
--
影响因子：
5.4
作者：
GUIDOTTI, LG;MATZKE, B;CHISARI, FV
通讯作者：
CHISARI, FV
DOI：
10.1073/pnas.84.4.1005
发表时间：
1987-02-01
影响因子：
11.1
作者：
SELLS, MA;CHEN, ML;ACS, G
通讯作者：
ACS, G
影响因子：
25.7
作者：
Lucifora, Julie;Arzberger, Silke;Protzer, Ulrike
通讯作者：
Protzer, Ulrike
影响因子：
3.7
作者：
Cavenaugh JS;Awi D;Mendy M;Hill AV;Whittle H;McConkey SJ
通讯作者：
McConkey SJ