Molecular Epidemiology & Bioinformatics Laboratory, Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, USA.
Sci Rep. 2012;2:267. doi: 10.1038/srep00267. Epub 2012 Feb 15.
Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development.
针对丙型肝炎病毒 (HCV) 的疫苗开发受到阻碍，原因是对定义不同表位之间交叉免疫反应性的因素了解不足。本研究采用合成肽和小鼠免疫作为模型，对 HCV 高变区 1 (HVR1) 的变体之间的交叉免疫反应性进行了定量分析。对 26883 对肽之间的 26883 种免疫反应进行分析表明，HVR1 变体之间的交叉免疫反应性呈偏态分布，少数变体的抗体与所有测试的肽反应。基于氨基酸序列可以准确地对 HVR1 交叉免疫反应性进行建模。所测试的肽被映射到 HVR1 序列空间中，该空间被可视化为由 11319 个序列组成的网络。网络中心性更高的 HVR1 变体表现出更广泛的交叉免疫反应性。每个 HCV 基因型和亚型都可以探索整个序列空间。这些发现表明 HVR1 抗原多样性广泛趋同且受到有效限制，这对疫苗开发具有重要意义。
