title: Diverse antigenic site targeting of influenza hemagglutinin in the murine antibody recall response to A(H1N1)pdm09 virus.
abstract: Here we define the epitopes on HA that are targeted by a group of 9 recombinant monoclonal antibodies (rmAbs) isolated from memory B cells of mice, immunized by infection with A(H1N1)pdm09 virus followed by a seasonal TIV boost. These rmAbs were all reactive against the HA1 region of HA, but display 7 distinct binding footprints, targeting each of the 4 known antigenic sites. Although the rmAbs were not broadly cross-reactive, a group showed subtype-specific cross-reactivity with the HA of A/South Carolina/1/18. Screening these rmAbs with a panel of human A(H1N1)pdm09 virus isolates indicated that naturally-occurring changes in HA could reduce rmAb binding, HI activity, and/or virus neutralization activity by rmAb, without showing changes in recognition by polyclonal antiserum. In some instances, virus neutralization was lost while both ELISA binding and HI activity were retained, demonstrating a discordance between the two serological assays traditionally used to detect antigenic drift.
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Jason R
authors: JR
authors: Wilson
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Zhu
authors: Z
authors: Guo
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Wen-Pin
authors: WP
authors: Tzeng
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Rebecca J
authors: RJ
authors: Garten
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Xu
authors: X
authors: Xiyan
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Elisabeth G
authors: EG
authors: Blanchard
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Kristy
authors: K
authors: Blanchfield
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: James
authors: J
authors: Stevens
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA.
authors: Jacqueline M
authors: JM
authors: Katz
authors: Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. Electronic address: ite1@cdc.gov.
authors: Ian A
authors: IA
authors: York
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D000940:Antigenic Variation / Q000235:genetics / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D001665:Binding Sites; D003429:Cross Reactions / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D051379:Mice; D008958:Models, Molecular; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000821:virology; D011485:Protein Binding; D011487:Protein Conformation; D011994:Recombinant Proteins
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011994:Recombinant Proteins
keywords: A/H1N1/pdm09; Antigenic drift; Antigenic site; Epitope mapping; Influenza; Monoclonal antibody; Virus neutralization