A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.
A hepatitis C virus (HCV) vaccine comprising envelope glycoproteins gpE1/gpE2 derived from a single isolate elicits broad cross-genotype neutralizing antibodies in humans.
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DOI：
10.1371/journal.pone.0059776
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Houghton M
中科院分区：
文献类型：
--
作者：
Law JL;Chen C;Wong J;Hockman D;Santer DM;Frey SE;Belshe RB;Wakita T;Bukh J;Jones CT;Rice CM;Abrignani S;Tyrrell DL;Houghton M
虽然治愈HCV的方法即将出现，但新兴的药物鸡尾酒将是昂贵的，与副作用和耐药性有关，考虑到估计世界各地的高感染率，全球疫苗成为当务之急。由于HCV的高度异质性，有效的HCV疫苗，可以引起广泛的交叉中和抗体已经代表了一个重大的挑战。在这项研究中，我们测试了交叉中和抗体的存在下，在人类志愿者免疫重组糖蛋白gpE 1/gpE 2来自一个单一的HCV株（HCV 1基因型1a）。在Huh-7.5人肝癌细胞培养物中使用表达来自所有已知主要基因型1-7的异源HCV毒株的结构蛋白的感染性重组HCV（HCV-HCV）测试交叉中和。疫苗接种诱导了针对异源HCV基因型1a病毒的显著中和抗体，该病毒代表北美最常见的基因型。在检测的16名疫苗接种者中，根据1a病毒强中和性选择了3名，用于检测广泛交叉中和反应。至少有1名疫苗接种者显示可引起对所有HCV基因型的广泛交叉中和。虽然只在少数接种者中观察到，但我们的研究结果证明了一个关键概念，即来自单一HCV毒株的疫苗可以引起针对所有已知主要HCV基因型的广泛交叉中和抗体，并为进一步开发针对这种常见全球病原体的人类疫苗提供了相当大的鼓励。
Although a cure for HCV is on the near horizon, emerging drug cocktails will be expensive, associated with side-effects and resistance making a global vaccine an urgent priority given the estimated high incidence of infection around the world. Due to the highly heterogeneous nature of HCV, an effective HCV vaccine which could elicit broadly cross-neutralizing antibodies has represented a major challenge. In this study, we tested for the presence of cross-neutralizing antibodies in human volunteers who were immunized with recombinant glycoproteins gpE1/gpE2 derived from a single HCV strain (HCV1 of genotype 1a). Cross neutralization was tested in Huh-7.5 human hepatoma cell cultures using infectious recombinant HCV (HCVcc) expressing structural proteins of heterologous HCV strains from all known major genotypes, 1–7. Vaccination induced significant neutralizing antibodies against heterologous HCV genotype 1a virus which represents the most common genotype in North America. Of the 16 vaccinees tested, 3 were selected on the basis of strong 1a virus neutralization for testing of broad cross-neutralizing responses. At least 1 vaccinee was shown to elicit broad cross-neutralization against all HCV genotypes. Although observed in only a minority of vaccinees, our results prove the key concept that a vaccine derived from a single strain of HCV can elicit broad cross-neutralizing antibodies against all known major genotypes of HCV and provide considerable encouragement for the further development of a human vaccine against this common, global pathogen.
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