title: Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity.
abstract: Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.
authors: Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.
authors: Zhi-Yong
authors: ZY
authors: Yang
authors: Chih-Jen
authors: CJ
authors: Wei
authors: Wing-Pui
authors: WP
authors: Kong
authors: Lan
authors: L
authors: Wu
authors: Ling
authors: L
authors: Xu
authors: David F
authors: DF
authors: Smith
authors: Gary J
authors: GJ
authors: Nabel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002236:Carbohydrate Conformation; D002460:Cell Line; D005260:Female; D005814:Genes, Viral; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D007252:Influenza Vaccines / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D011991:Receptors, Virus / Q000378:metabolism*; D012794:Sialic Acids / Q000378:metabolism*; D014611:Vaccination
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011991:Receptors, Virus; D012794:Sialic Acids; C109963:hemagglutinin, avian influenza A virus
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