Identification of Two Critical Neutralizing Epitopes in the Receptor Binding Domain of Hepatitis B Virus preS1
Identification of Two Critical Neutralizing Epitopes in the Receptor Binding Domain of Hepatitis B Virus preS1
复制标题
乙型肝炎病毒 preS1 受体结合域中两个关键中和表位的鉴定
DOI：
10.1128/jvi.01680-20
复制
发表时间：
2020
影响因子：
5.4
通讯作者：
Suzuki
中科院分区：
文献类型：
--
作者：
Yato Keigo;Onodera Taishi;Matsuda Mami;Moriyama Saya;Fujimoto Akira;Watashi Koichi;Aizaki Hideki;Tanaka Tomohisa;Moriishi Kohji;Nishitsuji Hironori;Shimotohno Kunitada;Tamura Koji;Takahashi Yoshimasa;Wakita Takaji;Muramatsu Masamichi;Kato Takanobu;Suzuki
B型肝炎病毒（HBV）感染是一个重大的公共卫生问题。人肝细胞通过HBV大包膜蛋白preS 1区与牛磺胆酸钠共转运多肽的结合感染HBV。虽然已经分离出几种识别preS 1受体结合结构域并中和HBV感染的单克隆抗体（MAb），但中和表位的细节尚不清楚。在这项研究中，我们产生了13个单克隆抗体针对preS 1受体结合域的preS 1特异性记忆B细胞来自DNA免疫小鼠。根据表位区域将MAb分为三组，指定表位I至III。病毒中和试验显示，识别表位I和III的单克隆抗体中和HBV感染，表明这些结构域是病毒中和的关键表位。此外，针对多种基因型HBV的中和测定揭示表位I是半泛基因型中和表位，而表位III是基因型特异性表位。我们还发现，针对preS 1的中和性单克隆抗体可以中和携带疫苗诱导的逃逸突变的HBV。这些发现提供了深入了解新的免疫预防的预防和治疗HBV infection.IMPORTANCEThe HBV前S1氨基酸2至47区（前S1/2-47）是必不可少的病毒结合牛磺胆酸钠共转运多肽。已经报道了几种靶向preS 1/2-47的单克隆抗体可以中和HBV感染;然而，preS 1/2-47中的哪个区域包含HBV感染的关键中和表位尚不清楚。在这里，我们产生了几个针对preS 1/2-47的单克隆抗体，我们发现，识别preS 1/2-47的N或C末端的单克隆抗体显着中和HBV感染。我们进一步证实了抗preS 1单克隆抗体对具有疫苗逃逸突变的HBV的中和活性。这些数据阐明了抗体表位和病毒中和活性之间的关系，并且还表明含有preS 1区的疫苗抗原克服目前包含小S蛋白的B型肝炎疫苗的弱点的潜在能力。
Hepatitis B virus (HBV) infection is a major public health problem. Human hepatocytes are infected with HBV via binding between the preS1 region in the large envelope protein of HBV and sodium taurocholate cotransporting polypeptide. Although several monoclonal antibodies (MAbs) that recognize the receptor binding domain in preS1 and neutralize HBV infection have been isolated, details of neutralizing epitopes are not understood. In this study, we generated 13 MAbs targeting the preS1 receptor binding domain from preS1-specific memory B cells derived from DNA-immunized mice. The MAbs were classified into three groups according to the epitope regions, designated epitopes I to III. A virus neutralization assay revealed that MAbs recognizing epitopes I and III neutralized HBV infection, suggesting that these domains are critical epitopes for viral neutralization. In addition, a neutralization assay against multiple genotypes of HBV revealed that epitope I is a semipangenotypic neutralizing epitope, whereas epitope III is a genotype-specific epitope. We also showed that neutralizing MAbs against preS1 could neutralize HBV bearing a vaccine-induced escape mutation. These findings provide insight into novel immunoprophylaxis for the prevention and treatment of HBV infection.IMPORTANCEThe HBV preS1 amino acid 2 to 47 region (preS1/2–47) is essential for virus binding to sodium taurocholate cotransporting polypeptide. Several MAbs targeting preS1/2–47 have been reported to neutralize HBV infection; however, which region in preS1/2–47 contains the critical neutralizing epitope(s) for HBV infection is unclear. Here, we generated several MAbs targeting preS1/2–47, and we found that MAbs recognizing the N or C terminus of preS1/2–47 remarkably neutralized HBV infection. We further confirmed the neutralizing activity of anti-preS1 MAbs against HBV with a vaccine escape mutation. These data clarified the relationship between the antibody epitope and the virus-neutralizing activity and also suggested the potential ability of a vaccine antigen containing the preS1 region to overcome the weakness of current hepatitis B vaccines comprising the small S protein.
登录
查看更多内容
影响因子：
5.6
作者：
Watashi K;Urban S;Li W;Wakita T
通讯作者：
Wakita T
尽管进行免疫预防但仍发生急性或慢性感染的婴儿的乙型肝炎病毒表面基因突变
影响因子：
13.5
作者：
H. Hsu;Mei‐Hwei Chang;Y. Ni;Hopi Lin;Sheng;Ding‐Shinn Chen
通讯作者：
Ding‐Shinn Chen
GWAS 确定了 HLA-DRB1-DQB1 单倍型和 BTNL2 基因与乙型肝炎疫苗反应的关联
DOI：
--
发表时间：
2017
期刊：
影响因子：
--
作者：
Nao Nishida;Masaya Sugiyama;Hiromi Sawai;Jun Ohashi;Seik-Soon Khor;Takayo Tsuchiura;Katsushi Tokunaga;Masashi Mizokami
通讯作者：
Masashi Mizokami
DOI：
10.1073/pnas.0308527100
发表时间：
2004-03-02
影响因子：
11.1
作者：
Huang, CC;Venturi, M;Kwong, PD
通讯作者：
Kwong, PD
通过抗 HBs/a 单克隆抗体对乙型肝炎疫苗中的组特异性 a 抗原进行定量。
DOI：
--
发表时间：
1997
期刊：
Biologicals : journal of the International Association of Biological Standardization
影响因子：
--
作者：
H. Yamamoto;T. Satoh;T. Kiyohara;A. Totsuka;Y. Moritsugu
通讯作者：
Y. Moritsugu