Department for Vaccine Clinical Evaluation, NHC Key Laboratory of Enteric Pathogenic Microbiology, Jlangsu Provincial Center for Diseases Control and Prevention, Nanjing, Jiangsu 210009, China.
Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical Collage (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing Key Laboratory for Animal Models of Emerging and Reemerging Infectious Diseases, Beijing 100101, China.
Chin Med J (Engl). 2022 Apr 5;135(7):799-805. doi: 10.1097/CM9.0000000000002001.
The new emerging avian influenza A H7N9 virus, causing severe human infection with a mortality rate of around 41%. This study aims to provide a novel treatment option for the prevention and control of H7N9.
H7 hemagglutinin (HA)-specific B cells were isolated from peripheral blood plasma cells of the patients previously infected by H7N9 in Jiangsu Province, China. The human monoclonal antibodies (mAbs) were generated by amplification and cloning of these HA-specific B cells. First, all human mAbs were screened for binding activity by enzyme-linked immunosorbent assay. Then, those mAbs, exhibiting potent affinity to recognize H7 HAs were further evaluated by hemagglutination-inhibiting (HAI) and microneutralization in vitro assays. Finally, the lead mAb candidate was selected and tested against the lethal challenge of the H7N9 virus using murine models.
The mAb 6-137 was able to recognize a panel of H7 HAs with high affinity but not HA of other subtypes, including H1N1 and H3N2. The mAb 6-137 can efficiently inhibit the HA activity in the inactivated H7N9 virus and neutralize 100 tissue culture infectious dose 50 (TCID50) of H7N9 virus (influenza A/Nanjing/1/2013) in vitro, with neutralizing activity as low as 78 ng/mL. In addition, the mAb 6-137 protected the mice against the lethal challenge of H7N9 prophylactically and therapeutically.
The mAb 6-137 could be an effective antibody as a prophylactic or therapeutic biological treatment for the H7N9 exposure or infection.
新型甲型 H7N9 禽流感病毒的出现，导致严重的人类感染，死亡率约为 41%。本研究旨在为 H7N9 的防控提供新的治疗选择。
从中国江苏省既往感染 H7N9 的患者外周血浆细胞中分离出 H7 血凝素（HA）特异性 B 细胞。通过扩增和克隆这些 HA 特异性 B 细胞，生成人源单克隆抗体（mAb）。首先，通过酶联免疫吸附试验筛选所有 mAb 的结合活性。然后，对那些能识别 H7 HA 并具有强大亲和力的 mAb 进一步通过血凝抑制（HAI）和微量中和试验进行评估。最后，选择先导 mAb 候选物，并在小鼠模型中针对 H7N9 病毒的致死性挑战进行测试。
mAb 6-137 能够高亲和力识别一组 H7 HA，但不能识别其他亚型的 HA，包括 H1N1 和 H3N2。mAb 6-137 可有效抑制 H7N9 病毒中 HA 的活性，并在体外中和 100 组织培养感染剂量 50（TCID50）的 H7N9 病毒（甲型流感/南京/2013 年），其中和活性低至 78ng/ml。此外，mAb 6-137 可预防和治疗性地保护小鼠免受 H7N9 的致死性挑战。
mAb 6-137 可作为预防或治疗性生物治疗 H7N9 暴露或感染的有效抗体。
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