The influenza virus neuraminidase (NA) is becoming a focus for novel vaccine designs. However, the epitopes of human anti-NA antibodies have been poorly defined. Using a panel of 10 anti-N2 monoclonal antibodies (MAbs) that bind the H3N2 virus A/Switzerland/9715293/2013, we generated five escape mutant viruses. These viruses contained mutations K199E/T, E258K, A272D, and S331N. We found that mutations at K199 and E258 had the largest impact on MAb binding, NA inhibition and neutralization activity. In addition, a natural isolate from the 2017-2018 season was found to contain the E258K mutation and was resistant to numerous antibodies tested. The mutation S331N, was identified in virus passaged in the presence of antibody; however, it had little impact on MAb activity and greatly decreased viral fitness. This information aids in identifying novel human MAb epitopes on the N2 and helps with the detection of antigenically drifted NAs.

中文翻译：

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N2 神经氨酸酶新抗体表位的鉴定和表征

流感病毒神经氨酸酶 (NA) 正成为新型疫苗设计的焦点。然而，人类抗 NA 抗体的表位定义不明确。使用一组 10 种结合 H3N2 病毒 A/瑞士/9715293/2013 的抗 N2 单克隆抗体 (MAb)，我们生成了五种逃逸突变病毒。这些病毒包含突变 K199E/T、E258K、A272D 和 S331N。我们发现 K199 和 E258 的突变对 MAb 结合、NA 抑制和中和活性的影响最大。此外，发现 2017-2018 季节的一种天然分离物含有 E258K 突变，并且对许多测试的抗体具有抗性。在存在抗体的情况下传代的病毒中鉴定了突变 S331N；然而，它对 MAb 活性几乎没有影响，并且大大降低了病毒适应性。