UNASSIGNED:消除慢性HBV/HDV感染仍然是一个重大的全球卫生挑战。针对过量的乙型肝炎表面抗原(HBsAg)释放可能提供了一个有趣的机会窗口,以打破免疫耐受并使用其他抗病毒药物实现功能治愈。
未经证实:我们评估了HBsAg特异性人单克隆抗体,作为预防或治疗策略的一部分,在细胞培养模型和人肝嵌合小鼠中针对HBV/HDV感染。为了评估预防效果,小鼠在感染HBV或HBV/HDV(合并感染和重叠感染设置)之前被动免疫。在接受4周治疗的HBV和HBV/HDV共感染的小鼠中评估治疗效果。病毒参数(HBVDNA,在小鼠血浆中评估HDVRNA和HBsAg)。
UASSIGNED:该抗体可以剂量依赖性方式有效预防HBV/HDV感染,IC50值为3.5ng/ml。被动免疫显示完全保护小鼠免受HBV和HBV/HDV共感染。此外,在HBV感染的小鼠中,HDV重复感染被完全预防或至少减弱。最后,在建立HBV/HDV感染的小鼠中的抗体治疗导致病毒血症的显着下降和伴随的治疗HBsAg下降,治疗停止后出现中度病毒反弹。
UNASSIGNED:我们提供了一个有价值的候选抗体的数据,可以补充其他抗病毒药物的策略,旨在实现慢性HBV和HDV感染的功能治愈。
未经证实:慢性感染HBV的患者最终可能会发展为肝癌,并且极有可能感染HDV,恶化并加速疾病进展。不幸的是,目前的治疗方法很少能从慢性感染患者中消除这两种病毒。在这项研究中,我们提供了一种新型抗体的数据,该抗体能够在具有人源化肝脏的小鼠模型中预防慢性HBV/HDV感染。此外,HBV/HDV感染小鼠的抗体治疗在治疗期间强烈减少病毒载量。该抗体是进一步临床开发的有价值的候选物。
UNASSIGNED: Elimination of chronic HBV/HDV infection remains a major global health challenge. Targeting excessive hepatitis B surface antigen (HBsAg) release may provide an interesting window of opportunity to break immune tolerance and to achieve a functional cure using additional antivirals.
UNASSIGNED: We evaluated a HBsAg-specific human monoclonal antibody, as part of either a prophylactic or therapeutic strategy, against HBV/HDV infection in cell culture models and in human-liver chimeric mice. To assess prophylactic efficacy, mice were passively immunized prior to infection with HBV or HBV/HDV (coinfection and superinfection setting). Therapeutic efficacy was assessed in HBV and HBV/HDV-coinfected mice receiving 4 weeks of treatment. Viral parameters (HBV DNA, HDV RNA and HBsAg) were assessed in mouse plasma.
UNASSIGNED: The antibody could effectively prevent HBV/HDV infection in a dose-dependent manner with IC50 values of ∼3.5 ng/ml. Passive immunization showed complete protection of mice from both HBV and HBV/HDV coinfection. Moreover, HDV superinfection was either completely prevented or at least attenuated in HBV-infected mice. Finally, antibody treatment in mice with established HBV/HDV infection resulted in a significant decline in viremia and a concomitant drop in on-treatment HBsAg, with a moderate viral rebound following treatment cessation.
UNASSIGNED: We present data on a valuable antibody candidate that could complement other antivirals in strategies aimed at achieving functional cure of chronic HBV and HDV infection.
UNASSIGNED: Patients chronically infected with HBV may eventually develop liver cancer and are at great risk of being superinfected with HDV, which worsens and accelerates disease progression. Unfortunately, current treatments can rarely eliminate both viruses from chronically infected patients. In this study, we present data on a novel antibody that is able to prevent chronic HBV/HDV infection in a mouse model with a humanized liver. Moreover, antibody treatment of HBV/HDV-infected mice strongly diminishes viral loads during therapy. This antibody is a valuable candidate for further clinical development.