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Antiviral Res. 2019 Jul 20;170:104564. doi: 10.1016/j.antiviral.2019.104564. [Epub ahead of print]
Rapid isolation of a potent human antibody against H7N9 influenza virus from an infected patient.
Li J1, Yang Y2, Wang M3, Ren X4, Yang Z5, Liu L6, Zhang G6, Chen Q1, Yang W7, Chen YH8, Wan X9.
Author information
Abstract
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 (Gly151→Arg151) and S152P (Ser152→Pro152) 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.
Copyright ? 2019 Elsevier B.V. All rights reserved.
KEYWORDS:
ADCC; Antigenic site A; H7N9; Human monoclonal antibody; Mass spectroscopy; Switched memory B cells
PMID: 31336147 DOI: 10.1016/j.antiviral.2019.104564
Rapid isolation of a potent human antibody against H7N9 influenza virus from an infected patient.
Li J1, Yang Y2, Wang M3, Ren X4, Yang Z5, Liu L6, Zhang G6, Chen Q1, Yang W7, Chen YH8, Wan X9.
Author information
Abstract
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 (Gly151→Arg151) and S152P (Ser152→Pro152) 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.
Copyright ? 2019 Elsevier B.V. All rights reserved.
KEYWORDS:
ADCC; Antigenic site A; H7N9; Human monoclonal antibody; Mass spectroscopy; Switched memory B cells
PMID: 31336147 DOI: 10.1016/j.antiviral.2019.104564