title: H3N2 Mismatch of 2014-15 Northern Hemisphere Influenza Vaccines and Head-to-head Comparison between Human and Ferret Antisera derived Antigenic Maps.
abstract: The poor performance of 2014-15 Northern Hemisphere (NH) influenza vaccines was attributed to mismatched H3N2 component with circulating epidemic strains. Using human serum samples collected from 2009-10, 2010-11 and 2014-15 NH influenza vaccine trials, we assessed their cross-reactive hemagglutination inhibition (HAI) antibody responses against recent H3 epidemic isolates. All three populations (children, adults, and older adults) vaccinated with the 2014-15 NH egg- or cell-based vaccine, showed >50% reduction in HAI post-vaccination geometric mean titers against epidemic H3 isolates from those against egg-grown H3 vaccine strain A/Texas/50/2012 (TX/12e). The 2014-15 NH vaccines, regardless of production type, failed to further extend HAI cross-reactivity against H3 epidemic strains from previous seasonal vaccines. Head-to-head comparison between ferret and human antisera derived antigenic maps revealed different antigenic patterns among representative egg- and cell-grown H3 viruses characterized. Molecular modeling indicated that the mutations of epidemic H3 strains were mainly located in antibody-binding sites A and B as compared with TX/12e. To improve vaccine strain selection, human serologic testing on vaccination-induced cross-reactivity need be emphasized along with virus antigenic characterization by ferret model.
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Hang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, 240 Wise Center, Mississippi State, MS 39762.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Wan
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Ye
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Ewan P
authors.initials: EP
authors.lastname: Plant
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Yangqing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, 240 Wise Center, Mississippi State, MS 39762.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Courtney
authors.initials: C
authors.lastname: Finch
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, 240 Wise Center, Mississippi State, MS 39762.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kawano
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Olga
authors.initials: O
authors.lastname: Zoueva
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Meng-Jung
authors.initials: MJ
authors.lastname: Chiang
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Xianghong
authors.initials: X
authors.lastname: Jing
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Zhengshi
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Anding
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration (CBER/FDA), 10903 New Hampshire Ave, Silver Spring, MD 20993.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhu
mesh_terms: D000328:Adult; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D002648:Child; D003429:Cross Reactions / Q000276:immunology; D005289:Ferrets / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007106:Immune Sera / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000378:metabolism*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D014611:Vaccination
chemical_list: D000956:Antigens, Viral; D007106:Immune Sera; D007252:Influenza Vaccines; D037102:Lectins; C112408:hemagglutinin I