A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy
A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy
复制标题
一种针对乙型肝炎表面抗原 C 端的广谱纳米抗体，用于治疗慢性乙型肝炎感染
DOI：
10.1016/j.antiviral.2022.105265
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发表时间：
2022-02-21
影响因子：
7.6
通讯作者：
Xia，Ningshao
中科院分区：
文献类型：
--
作者：
Wang，Yue;Mei，Yaxian;Xia，Ningshao
持续的病毒抑制和B型肝炎表面抗原（HBsAg）的丢失是慢性B型肝炎（CH B）的新治疗目标。抗体在治疗持续性B型肝炎病毒（HBV）感染中的作用一直受到关注。虽然免疫治疗有很大的希望，但在CHB中基于抗体的HBV预防和控制的挑战包括广泛的HBV抗原多样性和长期病毒抑制的需要。在这项研究中，我们鉴定了一种新的抗HBsAg纳米抗体（Nb），125 s，从HBsAg免疫的羊驼中分离，并证实其在体内具有良好的HBsAg清除能力和对三种HBV亚型的广谱治疗活性。此外，我们的特点是在C-末端的HBsAg表面基序从氨基酸157至174的一个新的表位。基于125 s的长期被动免疫程序在HBsAg清除和诱导细胞免疫应答方面是有效的，为CHB免疫治疗提供了有希望的前景。
Sustainable viral suppression with hepatitis B surface antigen (HBsAg) loss is the new treatment goal for chronic hepatitis B (CHB). The role of antibodies in therapies for persistent hepatitis B virus (HBV) infection has received constant attention. While immunotherapy holds great promise, challenges for the antibody-based prevention and control of HBV in CHB include broad HBV antigenic diversity and the need for long-term viral suppression. In this study, we identified a new anti-HBsAg nanobody (Nb), 125s, isolated from HBsAg-immunized alpaca and confirmed its excellent potency in HBsAg clearance and broad-spectrum therapeutic activity against three HBV subtypesin vivo. In addition, we characterized a novel epitope at the C-terminus of the HBsAg surface motif from amino acids 157 to 174. A 125s-based long-term passive immunization program was efficacious at HBsAg clearance and inducing cellular immune responses, offering a promising outlook for CHB immunotherapy.