title: Effect of receptor binding specificity on the immunogenicity and protective efficacy of influenza virus A H1 vaccines.
abstract: The biological basis for the poor immunogenicity of unadjuvanted avian influenza A virus vaccines in mammals is not well understood. Here, we mutated the hemagglutinin (HA) of two H1N1 virus vaccines to determine whether virus receptor binding specificity contributes to the low immunogenicity of avian influenza virus vaccines. Mutations were introduced into the HA of an avian influenza virus, A/Duck/New York/15024-21/96 (Dk/96) which switched the binding preference from α2,3- to α2,6-linked sialic acid (SA). A switch in receptor specificity of the human A/South Carolina/1/18 (SC/18) virus generated a mutant virus with α2,3 SA (avian) binding preference. Inactivated vaccines were generated and administered to mice and ferrets intramuscularly. We found that the vaccines with human receptor binding preference induced slightly higher antibody titers and cell-mediated immune responses compared to their isogenic viruses with avian receptor binding specificity. Upon challenge with DK/96 or SC18 virus, differences in lung virus titers between the vaccine groups with different receptor-binding specificities were minimal. Overall, our data suggest that receptor binding specificity contributes only marginally to the immunogenicity of avian influenza vaccines and that other factors may also be involved.
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States.
authors: Xiangjie
authors: X
authors: Sun
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States.
authors: Weiping
authors: W
authors: Cao
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States.
authors: Claudia
authors: C
authors: Pappas
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States.
authors: Feng
authors: F
authors: Liu
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States.
authors: Jacqueline M
authors: JM
authors: Katz
authors: Immunology and Pathogenesis Branch, Influenza Division, National Center for Immunology and Respiratory Diseases, Centers for Disease Control and Prevention, 1600 Clifton Road, MS: G16, Atlanta, GA 30333, United States. Electronic address: tft9@cdc.gov.
authors: Terrence M
authors: TM
authors: Tumpey
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000276:immunology; D005260:Female; D005289:Ferrets; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000821:virology; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid / Q000276:immunology; D011200:Poultry; D011201:Poultry Diseases / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology*; D013045:Species Specificity
chemical_list: D000914:Antibodies, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid
keywords: Immunogenicity; Inactivated whole virus vaccine; Influenza virus; Receptor binding specificity