Targeting multiple viral proteins is pivotal for sustained suppression of highly mutable viruses. In recent years, broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed, and antibody monotherapy has been tested in preclinical and clinical studies to treat or prevent influenza virus infection. However, the impact of dual neutralization of the hemagglutinin and neuraminidase on the course of infection, as well as its therapeutic potential, has not been thoroughly tested. For this purpose, we generated a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase of influenza viruses. We demonstrated that this bispecific antibody has a dual-antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over monoclonal antibody combination as it resulted an improved neutralization capacity and augmented the antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice, reduced mice mortality, and limited the virus mutation profile upon antibody administration. Thus, dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.

中文翻译：

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双特异性抗体对流感病毒血凝素和神经氨酸酶的双重中和可提高抗病毒活性


靶向多种病毒蛋白对于持续抑制高度可变的病毒至关重要。近年来，已经开发了针对流感病毒血凝素和神经氨酸酶糖蛋白的广泛中和抗体，并且抗体单药治疗已在临床前和临床研究中进行了治疗或预防流感病毒感染的测试。然而，血凝素和神经氨酸酶的双重中和对感染过程的影响及其治疗潜力尚未得到彻底测试。为此，我们制备了一种双特异性抗体，可中和流感病毒的血凝素和神经氨酸酶。我们证明这种双特异性抗体具有双重抗病毒活性，因为它可以阻断感染并防止后代病毒从受感染的细胞中释放。我们表明，双特异性抗体对血凝素和神经氨酸酶的双重中和优于单克隆抗体组合，因为它提高了中和能力并增强了抗体效应器功能。值得注意的是，双特异性抗体在流感病毒感染的小鼠中显示出增强的抗病毒活性，降低了小鼠死亡率，并限制了抗体给药后的病毒突变谱。因此，血凝素和神经氨酸酶的双重中和作用可有效控制流感病毒感染。