tetano
Editor, Senior Moderator
Cell Rep. 2019 Dec 24;29(13):4460-4470.e8. doi: 10.1016/j.celrep.2019.11.084. [h=1]Identification of Antibodies Targeting the H3N2 Hemagglutinin Receptor Binding Site following Vaccination of Humans.[/h]
Zost SJ[SUP]1[/SUP], Lee J[SUP]2[/SUP], Gumina ME[SUP]1[/SUP], Parkhouse K[SUP]1[/SUP], Henry C[SUP]3[/SUP], Wu NC[SUP]4[/SUP], Lee CD[SUP]4[/SUP], Wilson IA[SUP]5[/SUP], Wilson PC[SUP]3[/SUP], Bloom JD[SUP]6[/SUP], Hensley SE[SUP]7[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 2 Department of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA. 3 Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. 4 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 5 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 6 Department of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. 7 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: hensley@pennmedicine.upenn.edu.
[h=3]Abstract[/h] Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.
Copyright ? 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] antibodies; hemagglutinin; influenza; vaccine
PMID: 31875553 DOI: 10.1016/j.celrep.2019.11.084
Zost SJ[SUP]1[/SUP], Lee J[SUP]2[/SUP], Gumina ME[SUP]1[/SUP], Parkhouse K[SUP]1[/SUP], Henry C[SUP]3[/SUP], Wu NC[SUP]4[/SUP], Lee CD[SUP]4[/SUP], Wilson IA[SUP]5[/SUP], Wilson PC[SUP]3[/SUP], Bloom JD[SUP]6[/SUP], Hensley SE[SUP]7[/SUP].
[h=3]Author information[/h] 1 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. 2 Department of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA. 3 Department of Medicine, Section of Rheumatology, the Knapp Center for Lupus and Immunology, University of Chicago, Chicago, IL 60637, USA. 4 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 5 Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA; The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. 6 Department of Basic Sciences and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA; Howard Hughes Medical Institute, Seattle, WA 98109, USA. 7 Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: hensley@pennmedicine.upenn.edu.
[h=3]Abstract[/h] Antibodies targeting the receptor binding site (RBS) of the influenza virus hemagglutinin (HA) protein are usually not broadly reactive because their footprints are typically large and extend to nearby variable HA residues. Here, we identify several human H3N2 HA RBS-targeting monoclonal antibodies (mAbs) that are sensitive to substitutions in conventional antigenic sites and are therefore not broadly reactive. However, we also identify an H3N2 HA RBS-targeting mAb that is exceptionally broadly reactive despite being sensitive to substitutions in residues outside of the RBS. We show that similar antibodies are present at measurable levels in the sera of some individuals but that they are inefficiently elicited by conventional vaccines. Our data indicate that HA RBS-targeting antibodies can be effective against variable viral strains even when they are somewhat sensitive to substitutions in HA residues adjacent to the RBS.
Copyright ? 2019 The Author(s). Published by Elsevier Inc. All rights reserved.
[h=4]KEYWORDS:[/h] antibodies; hemagglutinin; influenza; vaccine
PMID: 31875553 DOI: 10.1016/j.celrep.2019.11.084