血凝素茎结合抗体通过 Fc 依赖性效应功能增强神经氨酸酶抑制剂对流感的疗效。
Hemagglutinin stalk-binding antibodies enhance effectiveness of neuraminidase inhibitors against influenza via Fc-dependent effector functions.
机构信息
Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
Michael G. DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON L8S 4K1, Canada; McMaster Immunology Research Centre, McMaster University, Hamilton, ON L8S 4K1, Canada; Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON L8S 4K1, Canada.
出版信息
Cell Rep Med. 2022 Aug 16;3(8):100718. doi: 10.1016/j.xcrm.2022.100718.
The conserved hemagglutinin stalk domain is an attractive target for broadly effective antibody-based therapeutics and next-generation universal influenza vaccines. Protection provided by hemagglutinin stalk-binding antibodies is principally mediated through activation of immune effector cells. Titers of stalk-binding antibodies are highly variable on an individual level and tend to increase with age as a result of increasing exposures to influenza virus. In our study, we show that stalk-binding antibodies cooperate with neuraminidase inhibitors to protect against influenza virus infection in an Fc-dependent manner. These data suggest that the effectiveness of neuraminidase inhibitors is likely influenced by an individual's titers of stalk-binding antibodies and that neuraminidase inhibitors may enhance the effectiveness of future stalk-binding monoclonal antibody-based treatments.
保守的血凝素茎域是一种有吸引力的广泛有效的抗体为基础的治疗和下一代通用流感疫苗的目标。血凝素茎结合抗体提供的保护主要是通过激活免疫效应细胞。茎结合抗体的滴度在个体水平上是高度可变的，并且随着年龄的增长而增加，这是由于接触流感病毒的增加。在我们的研究中，我们表明，茎结合抗体与神经氨酸酶抑制剂合作，以保护免受流感病毒感染的方式依赖于 Fc。这些数据表明，神经氨酸酶抑制剂的有效性可能受到个体的茎结合抗体滴度的影响，神经氨酸酶抑制剂可能增强未来茎结合单克隆抗体治疗的有效性。
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