Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination.
Clearing Persistent Extracellular Antigen of Hepatitis B Virus: An Immunomodulatory Strategy To Reverse Tolerance for an Effective Therapeutic Vaccination.
复制标题
DOI：
10.4049/jimmunol.1502061
复制
发表时间：
2016-04-01
期刊：
影响因子：
--
通讯作者：
Fu YX
中科院分区：
文献类型：
--
作者：
Zhu D;Liu L;Yang D;Fu S;Bian Y;Sun Z;He J;Su L;Zhang L;Peng H;Fu YX
由于HBV诱导的耐受性，控制慢性B型肝炎病毒（HBV）感染（CH B）的治疗性疫苗/策略的开发一直具有挑战性。在这项研究中，我们探讨了打破耐受和恢复耐受小鼠对HBV表面抗原的免疫应答的策略。我们证明，免疫耐受状态归因于HBV携带者模型中循环HBsAg的水平和持续时间。在耐受性小鼠中，通过单克隆抗HBsAg抗体去除循环中的HBsAg可以逐渐降低耐受性，并重建B细胞和CD 4 + T细胞对后续Engerix-B疫苗接种的反应，产生保护性IgG。此外，通过加入TLR激动剂诱导的HBsAg特异性CD 8 + T细胞导致血清和肝脏中HBV的清除。因此，保护性免疫的产生可以通过用中和抗体清除细胞外病毒抗原，然后接种疫苗来实现。
Development of therapeutic vaccines/strategies to control chronic hepatitis B virus (HBV) infection (CHB) has been challenging due to HBV-induced tolerance. In this study, we explored strategies for breaking tolerance and restoring the immune response to the HBV surface antigen in tolerant mice. We demonstrated that immune tolerance status is attributed to the level and duration of circulating HBsAg in HBV carrier models. Removal of circulating HBsAg by a monoclonal anti-HBsAg antibody in tolerant mice could gradually reduce tolerance and reestablish B cell and CD4+ T cell responses to subsequent Engerix-B vaccination, producing protective IgG. Furthermore, HBsAg-specific CD8+ T cells induced by the addition of a TLR agonist, resulted in clearance of HBV in both serum and liver. Thus, generation of protective immunity can be achieved by clearing extracellular viral antigen with neutralizing antibodies followed by vaccination.