MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS) and Comparative Medicine Center, Peking Union Medical Collage (PUMC), Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing, China.
Nat Commun. 2015 Mar 30;6:6714. doi: 10.1038/ncomms7714.
The recently identified avian-originated influenza H7N9 virus causes severe pulmonary disease and may lead to death in humans. Currently, treatment options for the prevention and control of fatal H7N9 infections in humans remain limited. Here we characterize two human monoclonal antibodies (HuMAbs), HNIgGA6 and HNIgGB5, by screening a Fab antibody phage library derived from patients who recovered from H7N9 infection. Both antibodies exhibit high neutralizing activity against H7N9 virus in cells. Two amino acids in the receptor-binding site, 186V and 226L, are crucial for the binding of these two HuMAbs to viral haemagglutinin antigens. Prophylaxis with HNIgGA6 and HNIgGB5 confers significant immunity against H7N9 virus in a mouse model and significantly reduces the pulmonary virus titre. When administered post infection, therapeutic doses of the HuMAbs also provide robust protection against lethality. These antibodies might represent a potential alternative or adjunct to H7N9 pandemic interventions.
最近发现的禽流感 H7N9 病毒可导致人类严重肺部疾病，并可能导致死亡。目前，预防和控制人类致命性 H7N9 感染的治疗选择仍然有限。在这里，我们通过筛选来自从 H7N9 感染中康复的患者的 Fab 抗体噬菌体文库，对两种人源单克隆抗体（HuMAb）HNIgGA6 和 HNIgGB5 进行了表征。这两种抗体在细胞中均表现出对 H7N9 病毒的高中和活性。受体结合部位的两个氨基酸，186V 和 226L，对这两种 HuMAb 与病毒血凝素抗原的结合至关重要。在小鼠模型中，用 HNIgGA6 和 HNIgGB5 进行预防可显著抵抗 H7N9 病毒，显著降低肺部病毒滴度。在感染后给药时，治疗剂量的抗体也能提供针对致死性的强大保护。这些抗体可能代表了 H7N9 大流行干预的一种潜在替代或辅助手段。
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