从一个新的乙肝病毒靶向免疫治疗通过T细胞来自患者感染不

StephenW

Vaccine. 2015 Jul 22. pii: S0264-410X(15)00954-8. doi: 10.1016/j.vaccine.2015.07.020. [Epub ahead of print]
Recognition of core-derived epitopes from a novel HBV-targeted immunotherapeutic by T-cells from patients infected by different viral genotypes.Godon O1, Evlachev A2, Bourgine M1, Meritet JF3, Martin P2, Inchauspe G2, Michel ML4.
Author information

• 1Laboratoire de Pathogenèse des virus de l'hépatite B, Institut Pasteur, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, Paris Cedex 15 75724, France.
• 2Transgene SA, Department of Infectious Diseases, Lyon, France.
• 3Virology Unit, Cochin Hospital, Paris, France.
• 4Laboratoire de Pathogenèse des virus de l'hépatite B, Institut Pasteur, Département de Virologie, Institut Pasteur, 28, rue du Docteur Roux, Paris Cedex 15 75724, France; INSERM U994, Département de Virologie, Institut Pasteur, Paris, France. Electronic address: [email protected].
  

AbstractHepatitis B virus (HBV) infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular carcinoma. Current therapies based on nucleos(t)ide analogs or pegylated-interferon-α lead to control of viral replication in most patients but rarely achieve cure. A potential strategy to control chronic hepatitis B is to restore or induce functional anti-HBV T-cell immune responses using HBV-specific immunotherapeutics. However, viral diversity is a challenge to the development of this class of products as HBV genotypes display a sequence diversity of up to 8%. We have developed a novel HBV-targeted immunotherapeutic, TG1050, based on a non-replicative Adenovirus vector encoding a unique and large fusion protein composed of multiple antigenic regions derived from a HBV genotype D sequence. Using peripheral blood mononuclear cells from 23 patients chronically infected by five distinct genotypes (gt A, B, C, D and E) and various sets of peptides encompassing conserved versus divergent regions of HBV core we have measured ability of TG1050 genotype D core-derived peptides to be recognized by T-cells from patients infected by various genotypes. Overall, PBMCs from 78% of genotype B or C- and 100% genotype A or E-infected patients lead to detection of HBV core-specific T-cells recognizing genotype D antigenic domains located both in conserved and variable regions. This proof-of-concept study supports the clinical development of TG1050 in large patient populations independently of infecting genotypes.
Copyright © 2015. Published by Elsevier Ltd.


KEYWORDS: Core protein; Genotypes; HBV; Immunotherapy; T-cell responses; Vaccine

StephenW

疫苗。 2015年22月PII：S0264-410X（15）00954-8。 DOI：10.1016 / j.vaccine.2015.07.020。 [打印EPUB的提前]
从一个新的乙肝病毒靶向免疫治疗通过T细胞来自患者感染不同的病毒基因型识别核心衍生的表位。
Godon O1，Evlachev A2，Bourgine M1，Meritet JF3，马丁P2，Inchauspe G2，米歇尔ML4。
作者信息

    1Laboratoire德宫Pathogenèse病毒DE L'hépatiteB，巴斯德研究所，DEPARTEMENT德Virologie，巴斯德研究所，28街杜法学博士卢，巴黎Cedex的15 75724，法国。
    2Transgene SA，传染病，法国里昂系。
    3Virology单位，科钦医院，巴黎，法国。
    4Laboratoire德宫Pathogenèse病毒DE L'hépatiteB，巴斯德研究所，DEPARTEMENT德Virologie，巴斯德研究所，28街杜法学博士卢，巴黎Cedex的15 75724，法国; INSERM U994，DEPARTEMENT德Virologie，巴斯德研究所，法国巴黎。电子地址：[email protected]。

抽象

乙型肝炎病毒（HBV）感染数以百万计的世界各地的人，是肝硬化和肝癌的主要原因。基于核苷（酸）类似物或聚乙二醇化干扰素-α导致病毒复制，大多数患者的控制，但很少达到根治目前的治疗方法。一个潜在的战略，以控制慢性乙肝是恢复或通过诱导HBV特异性免疫治疗功能性抗HBV的T细胞免疫反应。然而，病毒多样性是一个挑战为该类产品的开发作为HBV基因型显示高达8％的序列多样性。我们已经开发了一种新的乙肝病毒靶向免疫治疗，TG1050，基于非复制型腺病毒载体，它编码来自乙型肝炎病毒基因D序列衍生多抗原区域组成的独特和大的融合蛋白。利用慢性感染由五个不同的基因型（GT A，B，C，D和E）和各组肽的23例患者外周血单核细胞包围保守与HBV核心发散的区域，我们测量了TG1050 D型核心衍生的能力肽被T细胞从患者感染不同基因型识别。总体而言，来自基因型B或C和100％A基因型或E感染患者的78％的PBMC导致检测HBV核心特异性T细胞识别基因型位于既在保守区和可变区D抗原域。概念验证的这项研究支持TG1050的大型患者群体的独立基因型感染临床开发。

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关键词：

核心蛋白;基因型;乙肝病毒;免疫治疗; T细胞反应;疫苗

MP4

TG1050