Shenzhen Laboratory of Human Antibody Engineering, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Boulevard, University City of Shenzhen, Xili Nanshan, Shenzhen, 518055, China; School of Life Sciences, University of Chinese Academy of Sciences, No.19 (A) Yuquan Road, Shijingshan District, Beijing, 100049, PR China.
Shenzhen Key Laboratory of Pathogen and Immunity, Guangdong Key Laboratory for Diagnosis and Treatment of Emerging Infectious Diseases, State Key Discipline of Infectious Disease, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen Third People's Hospital, Shenzhen, 518112, China.
Antiviral Res. 2019 Oct;170:104564. doi: 10.1016/j.antiviral.2019.104564. Epub 2019 Jul 20.
Influenza virus A H7N9 remains a serious threat to public health due to the lack of effective vaccines and drugs. In this study, a neutralizing human antibody named 3L11 was rapidly isolated from the switched memory B cells of a patient infected with H7N9. The antibody 3L11 was encoded by the heavy-chain VH1-8 gene and the light-chain VL2-13 gene that had undergone somatic mutations, and conferred high affinity binding to H7N9 hemagglutinins (HAs). It promoted killing of infected cells by antibody-dependent cell-mediated cytotoxicity (ADCC). Epitope mapping by mass spectroscopy (MS) indicated that 3L11 bound to the peptide 149-175 of HAs that contained the 150-loop of the receptor-binding site (RBS). Additionally, the 3L11 escape strains had G151R (Gly→Arg) and S152P (Ser→Pro) mutations within a conserved antigenic site A near the RBS that were not observed in field strains. Importantly, 3L11 fully protected mice against a lethal H7N9 virus challenge, in both pre- and postexposure administration regimens. Altogether, this work demonstrates the feasibility of rapid isolation of neutralizing H7N9 antibodies from infected patients and provides a potential prophylactic and therapeutic agent against H7N9 viruses.
由于缺乏有效的疫苗和药物，甲型 H7N9 流感病毒仍然对公众健康构成严重威胁。在这项研究中，从感染 H7N9 的患者的转换记忆 B 细胞中快速分离出一种称为 3L11 的中和性人抗体。抗体 3L11 由经历体细胞突变的重链 VH1-8 基因和轻链 VL2-13 基因编码，并赋予对 H7N9 血凝素（HA）的高亲和力结合。它通过抗体依赖性细胞介导的细胞毒性（ADCC）促进感染细胞的杀伤。通过质谱（MS）进行的表位作图表明，3L11 结合到包含受体结合位点（RBS）的 150 环的 HA 的肽 149-175 上。此外，在 RBS 附近的保守抗原性位点 A 内，3L11 逃逸株具有 G151R（甘氨酸→精氨酸）和 S152P（丝氨酸→脯氨酸）突变，而在田间株中未观察到这些突变。重要的是，3L11 完全保护小鼠免受致死性 H7N9 病毒攻击，无论是在暴露前还是暴露后给药方案中。总的来说，这项工作证明了从感染患者中快速分离中和性 H7N9 抗体的可行性，并为 H7N9 病毒提供了一种潜在的预防性和治疗性药物。
