Subclade 2.2.1-Specific Human Monoclonal Antibodies That Recognize an Epitope in Antigenic Site A of Influenza A(H5) Virus HA Detected between 2015 and 2018
Subclade 2.2.1-Specific Human Monoclonal Antibodies That Recognize an Epitope in Antigenic Site A of Influenza A(H5) Virus HA Detected between 2015 and 2018
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DOI：
10.3390/v11040321
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发表时间：
2019-04-01
期刊：
影响因子：
4.7
通讯作者：
Kawaoka, Yoshihiro
中科院分区：
文献类型：
--
作者：
Okuda, Moe;Yamayoshi, Seiya;Kawaoka, Yoshihiro
高致病性H5禽流感病毒在世界各地的家禽和野鸟中持续存在。它们有时会引起鸟类和哺乳动物宿主之间的种间传播。在2015年至2018年期间，检测到具有子进化枝2.3.4.4、2.3.2.1、2.2.1或7.2 HA的H5病毒。为了了解H5-HA的中和表位，我们鉴定了15种针对H5病毒HA的人单克隆抗体（mAb），这些抗体从接受含有亚支2.2.1或2.1.3.2病毒作为抗原的H5 N1疫苗的志愿者获得。12种mAb对亚进化枝2.2.1的HA具有特异性，2种mAb对亚进化枝2.1.3.2的HA具有特异性，1种mAb对两者的HA都具有特异性。在分析的15种单克隆抗体中，9种特异于亚进化枝2.2.1的HA，并共享VH和VL基因，具有血凝抑制和中和活性，而其他则没有。在抗原位点A中的位置144-147处的单个氨基酸取代或插入赋予针对这九种mAb的针对亚进化枝2.2.1病毒的抗性。144-147位氨基酸在亚进化枝2.2.1中高度保守，但与其他亚进化枝的氨基酸不同。这些结果表明，包括144-147位氨基酸在内的中和表位是人抗体的靶向抗原，并且在亚进化枝2.2.1与其他亚进化枝之间的抗原差异中发挥作用。
Highly pathogenic avian H5 influenza viruses persist among poultry and wild birds throughout the world. They sometimes cause interspecies transmission between avian and mammalian hosts. H5 viruses possessing the HA of subclade 2.3.4.4, 2.3.2.1, 2.2.1, or 7.2 were detected between 2015 and 2018. To understand the neutralizing epitopes of H5-HA, we characterized 15 human monoclonal antibodies (mAbs) against the HA of H5 viruses, which were obtained from volunteers who received the H5N1 vaccine that contains a subclade 2.2.1 or 2.1.3.2 virus as an antigen. Twelve mAbs were specific for the HA of subclade 2.2.1, two mAbs were specific for the HA of subclade 2.1.3.2, and one mAb was specific for the HA of both. Of the 15 mAbs analyzed, nine, which were specific for the HA of subclade 2.2.1, and shared the VH and VL genes, possessed hemagglutination inhibition and neutralizing activities, whereas the others did not. A single amino acid substitution or insertion at positions 144-147 in antigenic site A conferred resistance against these nine mAbs to the subclade 2.2.1 viruses. The amino acids at positions 144-147 are highly conserved among subclade 2.2.1, but differ from those of other subclades. These results show that the neutralizing epitope including amino acids at positions 144-147 is targeted by human antibodies, and plays a role in the antigenic difference between subclade 2.2.1 and other subclades.