title: Mechanisms of hemagglutinin targeted influenza virus neutralization.
abstract: Human monoclonal antibodies have been identified which neutralize broad spectra of influenza A or B viruses. Here, we dissect the mechanisms by which such antibodies interfere with infectivity. We distinguish four mechanisms that link the conserved hemagglutinin (HA) epitopes of broadly neutralizing antibodies to critical processes in the viral life cycle. HA-stem binding antibodies can act intracellularly by blocking fusion between the viral and endosomal membranes and extracellularly by preventing the proteolytic activation of HA. HA-head binding antibodies prevent viral attachment and release. These insights into newly identified ways by which the human immune system can interfere with influenza virus infection may aid the development of novel universal vaccines and antivirals.
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Boerries
authors.initials: B
authors.lastname: Brandenburg
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Wouter
authors.initials: W
authors.lastname: Koudstaal
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Goudsmit
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Klaren
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Chan
authors.initials: C
authors.lastname: Tang
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Miriam V
authors.initials: MV
authors.lastname: Bujny
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Hans J W M
authors.initials: HJ
authors.lastname: Korse
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Ted
authors.initials: T
authors.lastname: Kwaks
authors.affiliation: Centre for Synthetic Biology, Zernike Institute for Advanced Materials, Groningen, The Netherlands ; Harvard Biophysics Program, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Otterstrom
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Jarek
authors.initials: J
authors.lastname: Juraszek
authors.affiliation: Centre for Synthetic Biology, Zernike Institute for Advanced Materials, Groningen, The Netherlands.
authors.forename: Antoine M
authors.initials: AM
authors.lastname: van Oijen
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Ronald
authors.initials: R
authors.lastname: Vogels
authors.affiliation: Crucell Vaccine Institute, Janssen Center of Excellence for Immunoprophylaxis, Leiden, The Netherlands.
authors.forename: Robert H E
authors.initials: RH
authors.lastname: Friesen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000276:immunology; D006388:Hemagglutinins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000939:Epitopes; D006388:Hemagglutinins