A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.
A human monoclonal antibody with neutralizing activity against highly divergent influenza subtypes.
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DOI：
10.1371/journal.pone.0028001
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Burioni R
中科院分区：
文献类型：
--
作者：
Clementi N;De Marco D;Mancini N;Solforosi L;Moreno GJ;Gubareva LV;Mishin V;Di Pietro A;Vicenzi E;Siccardi AG;Clementi M;Burioni R
对广谱抗甲型流感单克隆抗体（mAb）的兴趣最近通过鉴定具有异亚型中和活性的抗血凝素（HA）mAb而得到加强，所述抗血凝素（HA）mAb用于设计“通用”预防或治疗工具。然而，迄今为止描述的大多数单克隆抗体不结合和中和属于高度不同亚型的病毒分离株，所述高度不同亚型聚集成两个不同的基于HA的流感系统发生组：组1包括亚型H1、H2、H5和H9等，组2包括亚型H3等。在此，我们描述了一种名为PN-SIA 28的人单克隆抗体，能够结合和中和属于系统发育组1的所有测试分离株，包括H1N1、H2 N2、H5 N1和H9 N2亚型，以及属于组2的几种分离株，包括来自1968年大流行第一阶段的H3 N2分离株。因此，PN-SIA 28能够中和属于引起所有报告的大流行的亚型以及具有大流行潜力的其他亚型的分离株。PN-SIA 28识别的区域已在HA的茎区上鉴定，并且包括在不同流感亚型中高度保守的残基。PN-SIA 28特征的深入表征可能有助于改善现有的抗流感治疗策略，并可为开发通用疫苗策略提供新的工具。
The interest in broad-range anti-influenza A monoclonal antibodies (mAbs) has recently been strengthened by the identification of anti-hemagglutinin (HA) mAbs endowed with heterosubtypic neutralizing activity to be used in the design of “universal” prophylactic or therapeutic tools. However, the majority of the single mAbs described to date do not bind and neutralize viral isolates belonging to highly divergent subtypes clustering into the two different HA-based influenza phylogenetic groups: the group 1 including, among others, subtypes H1, H2, H5 and H9 and the group 2 including, among others, H3 subtype. Here, we describe a human mAb, named PN-SIA28, capable of binding and neutralizing all tested isolates belonging to phylogenetic group 1, including H1N1, H2N2, H5N1 and H9N2 subtypes and several isolates belonging to group 2, including H3N2 isolates from the first period of the 1968 pandemic. Therefore, PN-SIA28 is capable of neutralizing isolates belonging to subtypes responsible of all the reported pandemics, as well as other subtypes with pandemic potential. The region recognized by PN-SIA28 has been identified on the stem region of HA and includes residues highly conserved among the different influenza subtypes. A deep characterization of PN-SIA28 features may represent a useful help in the improvement of available anti-influenza therapeutic strategies and can provide new tools for the development of universal vaccinal strategies.