PDF(Pubmed)
Abstract：
The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here, we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2, or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 and BA.1 strains of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality but also for binding and neutralization of antigenically drifted viruses.
摘要：
抗体的恒定结构域对于效应子功能是重要的,但人们对它们如何影响病毒的结合和中和作用知之甚少。这里,我们评估了一组表达为IgG1,IgG2或IgG3的人流感病毒单克隆抗体(mAb).我们发现许多流感病毒特异性mAb具有改变的结合和中和能力,这取决于编码的IgG亚类,并且这些差异是由亚类的独特的二价能力引起的。重要的是,当通过抗原错配降低对靶抗原的亲和力时,抗体结合和中和的亚类差异最大.我们发现表达为IgG3的抗体更有效地结合并中和抗原性漂移的流感病毒。我们使用一组SARS-CoV-2特异性mAb和SARS-CoV-2的抗原高级B.1.351和BA.1菌株获得了类似的结果。我们发现，当表达为IgG3而不是IgG1时，获得许可的治疗性mAb保留了对SARS-CoV-2变体的中和宽度。这些数据突出显示,IgG亚类不仅对于微调效应子功能是重要的,而且对于结合和中和抗原性漂移的病毒也是重要的。
