新型DNA编码的单克隆抗体中和乙型肝炎病毒。

StephenW

Neutralization of Hepatitis B Virus by a Novel DNA-encoded Monoclonal Antibody
Urvi S Zankharia  1 , Sagar Kudchodkar  1 , Makan Khoshnejad  1 , Alfredo Perales-Puchalt  1 , Hyeree Choi  1 , Michelle Ho  1 , Faraz Zaidi  1 , Kenneth E Ugen  2 , Joseph J Kim  3 , David B Weiner  1 , Kar Muthumani  1
Affiliations
Affiliations

    1
    Vaccine & Immunotherapy Center, The Wistar Institute , Philadelphia, PA, USA.
    2
    Department of Molecular Medicine, University of South Florida Morsani College of Medicine , Tampa, FL, USA.
    3
    Inovio Pharmaceuticals, Plymouth Meeting , PA, USA.

    PMID: 32463327 DOI: 10.1080/21645515.2020.1763686

Abstract

Hepatitis B virus (HBV) causes a potentially life-threatening liver infection that frequently results in life-long chronic infection. HBV is responsible for 887,000 deaths each year, most resulting from chronic liver diseases and hepatocellular carcinoma. Presently, there are 250 million chronic HBV carriers worldwide who are at a high risk for developing cirrhosis and hepatocellular carcinoma (HCC). HCC is the most common type of liver cancer with a strong association with HBV infection. HBV transmission through blood transfusions and perinatal transfer from infected mother to child have been common routes of infection. In the present study, we describe the development of a synthetic DNA plasmid encoding an anti-HBV human monoclonal antibody specific for the common "a determinant region" of HBsAg of hepatitis B virus and demonstrate the ability of this platform at directing in vivo antibody expression. In vivo delivery of this DNA encoded monoclonal antibody (DMAb) plasmid in mice resulted in expression of human IgG over a period of one month following a single injection. Serum antibody was found to recognize the relevant conformational epitope from plasma purified native HBsAg as well as bound HBV in HepG2.2.15 cells. The serum DMAb efficiently neutralized HBV and prevented infection of HepaRG cells in vitro. Additional study of these HBV-DMAb as a possible therapy or immunoprophylaxis for HBV infection is warranted.

Keywords: DNA encoded monoclonal antibody (DMAb); Hepatitis B virus; immunoprophylaxis; neutralization.

StephenW

新型DNA编码的单克隆抗体中和乙型肝炎病毒。
Urvi S Zankharia 1，Sagar Kudchodkar 1，Makan Khoshnejad 1，Alfredo Perales-Puchalt 1，Hyeree Choi 1，Michelle Ho 1，Faraz Zaidi 1，Kenneth E Ugen 2，Joseph J Kim 3，David B Weiner 1，Kar Muthumani 1
隶属关系
隶属关系

    1个
    美国宾夕法尼亚州费城Wistar研究所疫苗和免疫治疗中心。
    2
    美国佛罗里达州坦帕市，南佛罗里达大学莫萨尼医学院，分子医学系。
    3
    Inovio Pharmaceuticals，美国宾夕法尼亚州普利茅斯会议。

    PMID：32463327 DOI：10.1080 / 21645515.2020.1763686

抽象

乙型肝炎病毒（HBV）可能危及生命，并可能导致终身慢性感染。 HBV每年导致887,000例死亡，其中大多数是由慢性肝病和肝细胞癌引起的。目前，全球有2.5亿慢性乙肝病毒携带者处于发展为肝硬化和肝细胞癌（HCC）的高风险中。 HCC是最常见的肝癌类型，与HBV感染密切相关。 HBV通过输血传播和围产期从受感染的母亲传给婴儿一直是常见的感染途径。在本研究中，我们描述了合成的DNA质粒的开发，该质粒编码对乙型肝炎病毒的HBsAg的常见“决定簇区域”具有特异性的抗HBV人单克隆抗体，并证明了该平台指导体内抗体表达的能力。单次注射后一个月内，这种DNA编码的单克隆抗体（DMAb）质粒在小鼠体内的递送导致人IgG的表达。发现血清抗体可识别血浆纯化的天然HBsAg以及HepG2.2.15细胞中结合的HBV的相关构象表位。血清DMAb有效中和了HBV，并在体外预防了HepaRG细胞的感染。这些HBV-DMAb作为HBV感染的可能疗法或免疫预防的进一步研究是必要的。

关键词：DNA编码的单克隆抗体（DMAb）；乙型肝炎病毒;免疫预防中和。

StephenW

https://www.tandfonline.com/doi/ ... eedAccess=true&

齐欢畅

这种DNA编码的单克隆抗体（DMAb）质粒在小鼠体内的递送导致人IgG的表达。发现血清抗体可识别血浆纯化的天然HBsAg以及HepG2.2.15细胞中结合的HBV的相关构象表位。血清DMAb有效中和了HBV，并在体外预防了HepaRG细胞的感染。这些HBV-DMAb作为HBV感染的可能疗法或免疫预防的进一步研究是必要的。

齐欢畅