title: Genetic versus antigenic differences among highly pathogenic H5N1 avian influenza A viruses: Consequences for vaccine strain selection.
abstract: Highly pathogenic H5N1 avian influenza A viruses display a remarkable genetic and antigenic diversity. We examined to what extent genetic distances between several H5N1 viruses from different clades correlate with antigenic differences and vaccine performance. H5-specific antisera were generated, and cross-reactivity and antigenic distances between 12 different viruses were determined. In general, antigenic distances increased proportional to genetic distances although notable exceptions were observed. Antigenic distances correlated better with genetic variation in 27 selected, antigenically-relevant H5 residues, than in the complete HA1 domain. Variation in these selected residues could accurately predict the antigenic distances for a novel H5N8 virus. Protection provided by vaccines against heterologous H5N1 challenge viruses indicated that cross-protection also correlates better with genetic variation in the selected antigenically-relevant residues than in complete HA1. When time is limited, variation at these selected residues may be used to accurately predict antigenic distance and vaccine performance.
authors.affiliation: Department of Virology, Wageningen Bioveterinary Research, Lelystad, The Netherlands. Electronic address: ben.peeters@wur.nl.
authors.forename: Ben
authors.initials: B
authors.lastname: Peeters
authors.affiliation: MSD Animal Health, Boxmeer, The Netherlands.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Reemers
authors.affiliation: Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Jos
authors.initials: J
authors.lastname: Dortmans
authors.affiliation: Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: de Vries
authors.affiliation: Department of Quantitative Veterinary Epidemiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Mart
authors.initials: M
authors.lastname: de Jong
authors.affiliation: MSD Animal Health, Boxmeer, The Netherlands.
authors.forename: Saskia
authors.initials: S
authors.lastname: van de Zande
authors.affiliation: Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands.
authors.forename: Peter J M
authors.initials: PJM
authors.lastname: Rottier
authors.affiliation: Department of Infectious Diseases & Immunology, Utrecht University, Utrecht, The Netherlands. Electronic address: C.A.M.deHaan@uu.nl.
authors.forename: Cornelis A M
authors.initials: CAM
authors.lastname: de Haan
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D000940:Antigenic Variation / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D002645:Chickens / Q000821:virology; D056738:Cross Protection / Q000276:immunology; D003429:Cross Reactions / Q000235:genetics / Q000276:immunology; D004285:Dogs; D014644:Genetic Variation / Q000235:genetics / Q000276:immunology; D057809:HEK293 Cells; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D061985:Madin Darby Canine Kidney Cells; D011201:Poultry Diseases / Q000821:virology; D012698:Serologic Tests; D061987:Sf9 Cells; D018411:Spodoptera; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines
keywords: Antigenic distance; Genetic variation; H5N1; Hemagglutinin; Influenza A virus; Vaccine performance