tetano
Editor, Senior Moderator
Cell Host Microbe. 2017 Sep 27. pii: S1931-3128(17)30344-X. doi: 10.1016/j.chom.2017.08.011. [Epub ahead of print]
[h=1]A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.[/h] Yu F[SUP]1[/SUP], Song H[SUP]2[/SUP], Wu Y[SUP]3[/SUP], Chang SY[SUP]4[/SUP], Wang L[SUP]3[/SUP], Li W[SUP]5[/SUP], Hong B[SUP]3[/SUP], Xia S[SUP]3[/SUP], Wang C[SUP]3[/SUP], Khurana S[SUP]6[/SUP], Feng Y[SUP]5[/SUP], Wang Y[SUP]5[/SUP], Sun Z[SUP]3[/SUP], He B[SUP]3[/SUP], Hou D[SUP]7[/SUP], Manischewitz J[SUP]6[/SUP], King LR[SUP]6[/SUP], Song Y[SUP]7[/SUP], Min JY[SUP]4[/SUP], Golding H[SUP]6[/SUP], Ji X[SUP]2[/SUP], Lu L[SUP]3[/SUP], Jiang S[SUP]3[/SUP], Dimitrov DS[SUP]5[/SUP], Ying T[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 ?) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] ADCC; H7N9 influenza; germline; hemagglutinin; monoclonal antibody
PMID: 28966056 DOI: 10.1016/j.chom.2017.08.011
[h=1]A Potent Germline-like Human Monoclonal Antibody Targets a pH-Sensitive Epitope on H7N9 Influenza Hemagglutinin.[/h] Yu F[SUP]1[/SUP], Song H[SUP]2[/SUP], Wu Y[SUP]3[/SUP], Chang SY[SUP]4[/SUP], Wang L[SUP]3[/SUP], Li W[SUP]5[/SUP], Hong B[SUP]3[/SUP], Xia S[SUP]3[/SUP], Wang C[SUP]3[/SUP], Khurana S[SUP]6[/SUP], Feng Y[SUP]5[/SUP], Wang Y[SUP]5[/SUP], Sun Z[SUP]3[/SUP], He B[SUP]3[/SUP], Hou D[SUP]7[/SUP], Manischewitz J[SUP]6[/SUP], King LR[SUP]6[/SUP], Song Y[SUP]7[/SUP], Min JY[SUP]4[/SUP], Golding H[SUP]6[/SUP], Ji X[SUP]2[/SUP], Lu L[SUP]3[/SUP], Jiang S[SUP]3[/SUP], Dimitrov DS[SUP]5[/SUP], Ying T[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The H7N9 influenza virus causes high-mortality disease in humans but no effective therapeutics are available. Here we report a human monoclonal antibody, m826, that binds to H7 hemagglutinin (HA) and protects against H7N9 infection. m826 binds to H7N9 HA with subnanomolar affinity at acidic pH and 10-fold lower affinity at neutral pH. The high-resolution (1.9 ?) crystal structure of m826 complexed with H7N9 HA indicates that m826 binds an epitope that may be fully exposed upon pH-induced conformational changes in HA. m826 fully protects mice against lethal challenge with H7N9 virus through mechanisms likely involving antibody-dependent cell-mediated cytotoxicity. Interestingly, immunogenetic analysis indicates that m826 is a germline antibody, and m826-like sequences can be identified in H7N9-infected patients, healthy adults, and newborn babies. These m826 properties offer a template for H7N9 vaccine immunogens, a promising candidate therapeutic, and a tool for exploring mechanisms of virus infection inhibition by antibodies.
Copyright ? 2017 Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] ADCC; H7N9 influenza; germline; hemagglutinin; monoclonal antibody
PMID: 28966056 DOI: 10.1016/j.chom.2017.08.011