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接种多表位融合蛋白后丙型肝炎病毒特异性细胞和体液免疫应答。

Hepatitis C virus-specific cellular and humoral immune responses following immunization with a multi-epitope fusion protein.

机构信息

Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, PR China.

出版信息

Int J Mol Med. 2012 Jan;29(1):12-7. doi: 10.3892/ijmm.2011.801. Epub 2011 Sep 28.

DOI:10.3892/ijmm.2011.801
PMID:21956746
Abstract

Hepatitis C virus (HCV) is an important causative agent of acute and chronic hepatitis worldwide. We prepared a fusion protein in the vector of pET-11d that included three conserved broadly neutralizing B-cell epitopes and a series of T-cell epitopes located in the HCV NS3 region. In vivo administration of this fusion construct resulted in specific CD8+ cytotoxic lymphocytes in both PBMCs and splenocytes that could recognize specific antigen sites that could be detected by FACS. An HCVcc system was established and applied to detect HCV-specific neutralizing antibodies. These results suggest that the multi-epitope fusion protein is immunogenic and can elicit both humoral and cellular immune responses. In particular, this fusion protein is able to elicit HCV-specific neutralizing antibodies, which are critical for viral clearance. This construct may be significant for vaccine development and could be a potential candidate to be included in the design of a prophylactic and therapeutic vaccine against HCV.

摘要

丙型肝炎病毒 (HCV) 是全球范围内引起急性和慢性肝炎的重要病原体。我们在 pET-11d 载体中制备了一种融合蛋白,该蛋白包含三个保守的广泛中和 B 细胞表位和位于 HCV NS3 区域的一系列 T 细胞表位。体内给予该融合构建物后,在 PBMC 和脾细胞中均能诱导出特异性的 CD8+细胞毒性淋巴细胞,这些淋巴细胞能够识别可以通过 FACS 检测到的特异性抗原位点。建立了 HCVcc 系统用于检测 HCV 特异性中和抗体。这些结果表明,多表位融合蛋白具有免疫原性,能够诱导体液和细胞免疫反应。特别是,该融合蛋白能够诱导 HCV 特异性中和抗体,这对于病毒清除至关重要。该构建物可能对疫苗开发具有重要意义,可能成为 HCV 预防性和治疗性疫苗设计的潜在候选物。

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