title: Combinatorial antibody libraries from survivors of the Turkish H5N1 avian influenza outbreak reveal virus neutralization strategies.
abstract: The widespread incidence of H5N1 influenza viruses in bird populations poses risks to human health. Although the virus has not yet adapted for facile transmission between humans, it can cause severe disease and often death. Here we report the generation of combinatorial antibody libraries from the bone marrow of five survivors of the recent H5N1 avian influenza outbreak in Turkey. To date, these libraries have yielded >300 unique antibodies against H5N1 viral antigens. Among these antibodies, we have identified several broadly reactive neutralizing antibodies that could be used for passive immunization against H5N1 virus or as guides for vaccine design. The large number of antibodies obtained from these survivors provide a detailed immunochemical analysis of individual human solutions to virus neutralization in the setting of an actual virulent influenza outbreak. Remarkably, three of these antibodies neutralized both H1 and H5 subtype influenza viruses.
authors.affiliation: Sea Lane Biotechnologies, 1455 Adams Drive, Menlo Park, CA 94025-1438, USA.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Kashyap
authors.forename: John
authors.initials: J
authors.lastname: Steel
authors.forename: Ahmet F
authors.initials: AF
authors.lastname: Oner
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dillon
authors.forename: Ryann E
authors.initials: RE
authors.lastname: Swale
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Wall
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Perry
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Faynboym
authors.forename: Mahmut
authors.initials: M
authors.lastname: Ilhan
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.forename: Lawrence
authors.initials: L
authors.lastname: Horowitz
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Ramesh R
authors.initials: RR
authors.lastname: Bhatt
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lerner
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D001717:Birds / Q000276:immunology / Q000821:virology; D018929:Cell Culture Techniques; D003429:Cross Reactions; D004196:Disease Outbreaks / Q000517:prevention & control*; D004285:Dogs; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007116:Immunization, Passive / Q000379:methods*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D009154:Mutation; D009500:Neutralization Tests; D019151:Peptide Library; D011487:Protein Conformation; D014421:Turkey / Q000453:epidemiology
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D019151:Peptide Library