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Perspectives for a vaccine against hepatitis delta virus

机译:预防丙型肝炎病毒疫苗的前景

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Hepatitis delta virus (HDV) causes severe hepatitis in carriers of hepatitis B virus (HBV). In ~90% of patients, HDV persists together with HBV and causes early development of cirrhosis and liver carcinoma. Worldwide ~15 million people are coinfected with HBV-HDV. Specific defects in the immune response causing persistence of the virus have not been identified. Several approaches to develop a vaccine to prevent superinfection in the preclinical model of the woodchuck have failed. Recent findings show that a DNA prime and viral vectors boost immunization regimen can induce a HDV specific CD8 T cell response and can prevent HDV infection in simultaneous infection of woodchuck hepatitis virus-HDV. The vaccine-induced specific CD8 T cell response is effective in preventing HDV replication and spread in the liver. However, the perspectives for a HDV vaccine against genotype-1 to prevent superinfection are much less promising. The T-cell response induced by the current DNA prime and viral vector boost immunization in the preclinical woodchuck model seems insufficient to prevent the spread of HDV in chronic HBV carriers. A more potent vaccine and repeated vaccinations are necessary to induce a HDV-specific T-cell response, which may prevent superinfection in HBsAg carriers.
机译:三角洲肝炎病毒(HDV)在乙肝病毒(HBV)携带者中引起严重肝炎。在约90%的患者中,HDV与HBV并存并导致肝硬化和肝癌的早期发展。全世界约有1500万人感染了HBV-HDV。尚未确定引起病毒持久的免疫应答中的特定缺陷。开发用于预防土拨鼠临床前模型中的过度感染的疫苗的几种方法均告失败。最近的发现表明,DNA初免和病毒载体增强免疫方案可以诱导HDV特异性CD8 T细胞应答,并可以在同时感染土拨鼠肝炎病毒-HDV的过程中预防HDV感染。疫苗诱导的特异性CD8 T细胞反应可有效预防HDV复制和在肝脏中扩散。然而,针对基因型1的HDV疫苗预防过度感染的观点远没有那么有前途。在临床前土拨鼠模型中,当前的DNA初免和病毒载体加强免疫诱导的T细胞反应似乎不足以阻止HDV在慢性HBV携带者中传播。为了诱导HDV特异性T细胞反应,需要更有效的疫苗和反复的疫苗接种,这可能会阻止HBsAg携带者的过度感染。

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