title: Cross-immunity Against Avian Influenza A(H7N9) Virus in the Healthy Population Is Affected by Antigenicity-Dependent Substitutions.
abstract: BACKGROUND
  The emergence of infections by the novel avian influenza A(H7N9) virus has posed a threat to human health. Cross-immunity between A(H7N9) and other heterosubtypic influenza viruses affected by antigenicity-dependent substitutions needs to be investigated.
  
  
  METHODS
  We investigated the cellular and humoral immune responses against A(H7N9) and 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09), by serological and T-cell-specific assays, in a healthy population. The molecular bases of the cellular and humoral antigenic variability of A(H7N9) were illuminated by structural determination.
  
  
  RESULTS
  We not only found that antibodies against A(H7N9) were lacking in the studied population, but also revealed that both CD4+and CD8+T cells that cross-reacted with A(H7N9) were at significantly lower levels than those against the A(H1N1)pdm09 peptides with substitutions. Moreover, individual peptides for A(H7N9) with low cross-reactivity were identified. Structural determination indicated that substitutions within these peptides influence the antigenic variability of A(H7N9) through both major histocompatibility complex (MHC) binding and T-cell receptor docking.
  
  
  CONCLUSIONS
  The impact of antigenicity-dependent substitutions on cross-reactivity of T-cell immunity against the novel influenza virus A(H7N9) in the healthy population benefits the understanding of immune evasion of influenza viruses and provides a useful reference for universal vaccine development.
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.|College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou.
authors.forename: William J
authors.initials: WJ
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.|University of Chinese Academy of Sciences, Beijing.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Tan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.|University of Chinese Academy of Sciences, Beijing.
authors.forename: Min
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.
authors.forename: Chuansong
authors.initials: C
authors.lastname: Quan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Yuhai
authors.initials: Y
authors.lastname: Bi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wu
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Laboratory of Protein Engineering and Vaccine, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Xiao
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Qi
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Yan
authors.affiliation: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: Division of Infectious Disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention.
authors.forename: Hongjie
authors.initials: H
authors.lastname: Yu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.
authors.forename: Guizhen
authors.initials: G
authors.lastname: Wu
authors.affiliation: Key Laboratory of Medical Virology, Ministry of Health, National Institute for Viral Disease Control and Prevention.|CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology.|Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences.|University of Chinese Academy of Sciences, Beijing.|College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou.
authors.forename: George F
authors.initials: GF
authors.lastname: Gao
mesh_terms: D000220:Adaptation, Biological; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D001782:Blood Donors; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D003429:Cross Reactions; D040961:Genetic Drift; D064368:Healthy Volunteers; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral
keywords: T-cell response; antigenic variation; avian influenza A(H7N9) virus; cross-reactivity; structure