title: Development and characterization of a panel of cross-reactive monoclonal antibodies generated using H1N1 influenza virus.
abstract: To characterize the antigenic epitopes of the hemagglutinin (HA) protein of H1N1 influenza virus, a panel consisting of 84 clones of murine monoclonal antibodies (mAbs) were generated using the HA proteins from the 2009 pandemic H1N1 vaccine lysate and the seasonal influenza H1N1(A1) vaccines. Thirty-three (39%) of the 84 mAbs were found to be strain-specific, and 6 (7%) of the 84 mAbs were subtype-specific. Twenty (24%) of the 84 mAbs recognized the common HA epitopes shared by 2009 pandemic H1N1, seasonal A1 (H1N1), and A3 (H3N2) influenza viruses. Twenty-five of the 84 clones recognized the common HA epitopes shared by the 2009 pandemic H1N1, seasonal A1 (H1N1) and A3 (H3N2) human influenza viruses, and H5N1 and H9N2 avian influenza viruses. We found that of the 16 (19%) clones of the 84 mAbs panel that were cross-reactive with human respiratory pathogens, 15 were made using the HA of the seasonal A1 (H1N1) virus and 1 was made using the HA of the 2009 pandemic H1N1 influenza virus. Immunohistochemical analysis of the tissue microarray (TMA) showed that 4 of the 84 mAb clones cross-reacted with human tissue (brain and pancreas). Our results indicated that the influenza virus HA antigenic epitopes not only induce type-, subtype-, and strain-specific monoclonal antibodies against influenza A virus but also cross-reactive monoclonal antibodies against human tissues. Further investigations of these cross-reactive (heterophilic) epitopes may significantly improve our understanding of viral antigenic variation, epidemics, pathophysiologic mechanisms, and adverse effects of influenza vaccines.
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Chun-yan
authors.initials: CY
authors.lastname: Guo
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Yi-gui
authors.initials: YG
authors.lastname: Tang
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Zong-li
authors.initials: ZL
authors.lastname: Qi
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Xiang-rong
authors.initials: XR
authors.lastname: Zhao
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Xue-ping
authors.initials: XP
authors.lastname: Huo
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Feng
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Peng-hua
authors.initials: PH
authors.lastname: Zhao
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China.
authors.forename: Hai-fang
authors.initials: HF
authors.lastname: Wang
authors.affiliation: Central Lab of Shaanxi Provincial People's Hospital, The Third Affiliated Hospital of the Medical College of Xi'an Jiaotong University, Key Laboratory of Infection and Immunity Disease of Shaanxi Province, Xi'an 710068, China. Electronic address: hjj6562@63.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Hu
authors.affiliation: Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, United States.
authors.forename: Xin-jian
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D018604:Epitope Mapping; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology*; D051379:Mice; D046888:Tissue Array Analysis
chemical_list: D000911:Antibodies, Monoclonal; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D016056:Immunodominant Epitopes; D007252:Influenza Vaccines
keywords: H1N1; HA protein; Human tissues, Heterophilic antigen epitopes; Influenza virus