Wilson Jason R, Guo Zhu, Tzeng Wen-Pin, Garten Rebecca J, Xiyan Xu, Blanchard Elisabeth G, Blanchfield Kristy, Stevens James, Katz Jacqueline M, York Ian A
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
Virology. 2015 Nov;485:252-62. doi: 10.1016/j.virol.2015.08.004. Epub 2015 Aug 27.
Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift.
在此，我们定义了甲型流感病毒血凝素（HA）上的表位，这些表位是由一组9种重组单克隆抗体（rmAb）靶向的，这些抗体从感染A（H1N1）pdm09病毒后再用季节性流感病毒裂解疫苗加强免疫的小鼠记忆B细胞中分离得到。这些rmAb均与HA的HA1区域发生反应，但显示出7种不同的结合足迹，靶向4个已知抗原位点中的每一个。尽管这些rmAb没有广泛的交叉反应性，但一组rmAb与A/南卡罗来纳州/1/18的HA具有亚型特异性交叉反应性。用一组人A（H1N1）pdm09病毒分离株筛选这些rmAb表明，HA的自然发生变化可降低rmAb的结合、血凝抑制（HI）活性和/或rmAb的病毒中和活性，而多克隆抗血清的识别没有变化。在某些情况下，病毒中和作用丧失，而酶联免疫吸附测定（ELISA）结合和HI活性均保留，这表明传统上用于检测抗原漂移的两种血清学检测方法之间存在不一致。
