神经氨酸酶
病毒学
血凝素(流感)
病毒
中和
抗体
生物
甲型流感病毒
单克隆抗体
神经氨酸酶抑制剂
免疫学
医学
2019年冠状病毒病(COVID-19)
病理
传染病(医学专业)
疾病
作者
Romila Moirangthem,Sapir Cordela,Dina Khateeb,Ben Shor,Ivan Košík,Dina Schneidman‐Duhovny,Michal Mandelboim,Friederike Jönsson,Jonathan W. Yewdell,Timothée Bruel,Yotam Bar‐On
标识
DOI:10.1016/j.ymthe.2024.07.023
摘要
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.
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