Huang D, Sansas B, Jiang J H, Gong Q M, Jin G D, Calais V, Yu D M, Zhu M Y, Wei D, Zhang D H, Inchauspé G, Zhang X X, Zhu R
Department of Infectious Diseases, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
Transgene S.A. Smart Data Lab, Illkirch Graffenstaden, France.
J Viral Hepat. 2017 Nov;24 Suppl 1:66-74. doi: 10.1111/jvh.12791.
Chronic hepatitis B (CHB) is one of the major public health challenges in the world. Due to a strong interplay between specific T-cell immunity and elimination of hepatitis B virus (HBV), efforts to develop novel immunotherapeutics are gaining attention. TG1050, a novel immunotherapy, has shown efficacy in an animal study. To support the clinical development of TG1050 in China, specific immunity to the fusion antigens of TG1050 was assessed in Chinese patients. One hundred and thirty subjects were divided into three groups as CHB patients, HBV spontaneous resolvers, and CHB patients with HBsAg loss after antiviral treatment. HBV-specific T-cell responses to pools of HBV Core or Polymerase genotype D peptides included in TG1050 were evaluated. HBV Core- or Polymerase-specific cells were detected in peripheral blood mononuclear cells (PBMCs) from the different cohorts. The frequencies and intensities of HBV Core-specific immune responses were significantly lower in CHB patients than in HBsAg loss subjects. In CHB patients, a dominant pool derived from Polymerase (Pol1) was the most immunogenic. CHB patients with low viral loads (<10 IU/mL) were more likely to have a positive response specific to the Core peptide pool. Overall, genotype D-derived peptides included in TG1050 could raise broad and functional T-cell responses in PBMCs from Chinese CHB patients infected with genotype B/C isolates. Core-specific immunogenic domains appeared as "hot spots" with the capacity to differentiate between CHB vs HBsAg loss subjects. These observations support the extended application and associated immune monitoring of TG1050 in China.
慢性乙型肝炎（CHB）是全球主要的公共卫生挑战之一。由于特异性T细胞免疫与乙型肝炎病毒（HBV）清除之间存在强烈的相互作用，开发新型免疫疗法的努力正受到关注。新型免疫疗法TG1050在一项动物研究中已显示出疗效。为支持TG1050在中国的临床开发，对中国患者中针对TG1050融合抗原的特异性免疫进行了评估。130名受试者被分为三组，分别为CHB患者、HBV自然清除者以及抗病毒治疗后HBsAg消失的CHB患者。评估了对TG1050中包含的HBV核心或聚合酶D基因型肽库的HBV特异性T细胞反应。在来自不同队列的外周血单个核细胞（PBMC）中检测到了HBV核心或聚合酶特异性细胞。CHB患者中HBV核心特异性免疫反应的频率和强度显著低于HBsAg消失的受试者。在CHB患者中，来自聚合酶（Pol1）的一个优势肽库免疫原性最强。病毒载量低（<10 IU/mL）的CHB患者对核心肽库产生阳性反应的可能性更高。总体而言，TG1050中包含的D基因型衍生肽可在感染B/C基因型分离株的中国CHB患者的PBMC中引发广泛且具有功能的T细胞反应。核心特异性免疫原性结构域表现为“热点”，能够区分CHB患者与HBsAg消失的受试者。这些观察结果支持TG1050在中国的扩展应用及相关免疫监测。
