title: Induction of Broadly Cross-Reactive Stalk-Specific Antibody Responses to Influenza Group 1 and Group 2 Hemagglutinins by Natural H7N9 Virus Infection in Humans.
abstract: The outbreak of novel avian H7N9 influenza virus infections in China in 2013 has demonstrated the continuing threat posed by zoonotic pathogens. Deciphering the immune response during natural infection will guide future vaccine development.
  
  
  
  We assessed the induction of heterosubtypic cross-reactive antibodies induced by H7N9 infection against a large panel of recombinant hemagglutinins and neuraminidases by quantitative enzyme-linked immunosorbent assay, and novel chimeric hemagglutinin constructs were used to dissect the anti-stalk or -head humoral immune response.
  
  
  
  H7N9 infection induced strong antibody responses against divergent H7 hemagglutinins. Interestingly, we also found induction of antibodies against heterosubtypic hemagglutinins from both group 1 and group 2 and a boost in heterosubtypic neutralizing activity in the absence of hemagglutination inhibitory activity. Kinetic monitoring revealed that heterosubtypic binding/neutralizing antibody responses typically appeared and peaked earlier than intrasubtypic responses, likely mediated by memory recall responses.
  
  
  
  Our results indicate that cross-group binding and neutralizing antibody responses primarily targeting the stalk region can be elicited after natural influenza virus infection. These data support our understanding of the breadth of the postinfection immune response that could inform the design of future, broadly protective influenza virus vaccines.
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Raffael
authors.initials: R
authors.lastname: Nachbagauer
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Lingyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Xinci
authors.initials: X
authors.lastname: Xie
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jin
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Anli
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Hirsh
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Di
authors.initials: D
authors.lastname: Tian
authors.affiliation: VacDiagn Biotechnology, Suzhou, Jiangsu, China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Shi
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Zhaoguang
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Songhua
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, USA.
authors.forename: Florian
authors.initials: F
authors.lastname: Krammer
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Key Laboratory of Medical Molecular Virology of Ministry of Education/Health, Shanghai Medical College, Fudan University, China.
authors.forename: Jianqing
authors.initials: J
authors.lastname: Xu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology*; D000917:Antibody Formation; D000918:Antibody Specificity; D002681:China / Q000453:epidemiology; D003429:Cross Reactions; D004196:Disease Outbreaks; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C483468:hemagglutinin, human influenza A virus
keywords: H7N9; cross-reactive antibody; influenza; stalk-reactive; universal influenza vaccine