Antigenic cartography of H1N1 influenza viruses using sequence-based antigenic distance calculation.

Antigenic cartography of H1N1 influenza viruses using sequence-based antigenic distance calculation.
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DOI:
10.1186/s12859-018-2042-4
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发表时间:
2018-02-12
期刊:
影响因子:
3
通讯作者:
Topham DJ
Topham DJ
中科院分区:
生物学4区
文献类型:
--
作者:
Anderson CS;McCall PR;Stern HA;Yang H;Topham DJ

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流感病毒序列数据可以很容易地用于估计毒株之间的抗原关系,并且存在包含数十万流感毒株序列数据的数据库,这使得基于序列的抗原距离估计对研究人员来说是一种有吸引力的方法。流行毒株与疫苗毒株之间的抗原不匹配导致疫苗有效性显著降低。此外,疫苗株与个体最初启动的菌株之间的抗原相关性可以影响抗体反应的交叉反应性。因此,了解已传播的流感病毒之间的抗原关系对疫苗学家和免疫学家都很重要。在这里,我们开发了一种使用基于序列的抗原距离方法(SBM)绘制流感病毒染色之间抗原关系的方法。我们使用了改良版的基于p-all表位序列的抗原距离计算,该计算利用流感血凝素(HA)遗传编码序列数据确定菌株之间的抗原相关性,并为p-all表位计算提供了实验验证。我们计算了1918年至2016年间从感染人类中分离的4838种H1N1病毒之间的抗原距离。我们首次证明,基于序列的H1N1流感病毒抗原距离可以使用经典的多维尺度在二维抗原制图中准确地表示。此外,该模型正确预测交叉反应抗体水平的下降,准确率为87%,即使使用少量序列,也具有很高的可重复性。这项工作提供了一个高度准确和精确的生物信息学工具,可用于评估免疫风险以及设计优化的疫苗接种策略。SBM利用HA序列数据准确估计菌株间的抗原性关系。H1N1病毒株的抗原性图显示,毒株的聚类抗原性与已报道的H3N2病毒相似。此外,我们证明了不同抗原位点的遗传变异不同,并讨论了其含义。本文的在线版本(10.1186/s12859-018-2042-4)包含补充材料,授权用户可使用。
The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response. Thus, understanding the antigenic relationships between influenza viruses that have circulated is important to both vaccinologists and immunologists. Here we develop a method of mapping antigenic relationships between influenza virus stains using a sequence-based antigenic distance approach (SBM). We used a modified version of the p-all-epitope sequence-based antigenic distance calculation, which determines the antigenic relatedness between strains using influenza hemagglutinin (HA) genetic coding sequence data and provide experimental validation of the p-all-epitope calculation. We calculated the antigenic distance between 4838 H1N1 viruses isolated from infected humans between 1918 and 2016. We demonstrate, for the first time, that sequence-based antigenic distances of H1N1 Influenza viruses can be accurately represented in 2-dimenstional antigenic cartography using classic multidimensional scaling. Additionally, the model correctly predicted decreases in cross-reactive antibody levels with 87% accuracy and was highly reproducible with even when small numbers of sequences were used. This work provides a highly accurate and precise bioinformatics tool that can be used to assess immune risk as well as design optimized vaccination strategies. SBM accurately estimated the antigenic relationship between strains using HA sequence data. Antigenic maps of H1N1 virus strains reveal that strains cluster antigenically similar to what has been reported for H3N2 viruses. Furthermore, we demonstrated that genetic variation differs across antigenic sites and discuss the implications. The online version of this article (10.1186/s12859-018-2042-4) contains supplementary material, which is available to authorized users.
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发表时间: 2013-07-29
期刊: The Journal of experimental medicine
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