title: Differential Effects of Prior Influenza Exposures on H3N2 Cross-reactivity of Human Postvaccination Sera.
abstract: BACKGROUND
  Effectiveness of seasonal influenza vaccines mainly depends upon how well vaccine strains represent circulating viruses; mismatched strains can lead to reduced protection. Humans have complex influenza exposure histories that increase with age, which may lead to different postvaccination responses to emerging influenza variants. Recent observational studies also suggest that prior vaccination may influence the performance of current seasonal vaccines.
  
  
  METHODS
  To elucidate the effects of age and influenza preexposures on cross-reactivity of vaccination-induced human antibodies, we generated antigenic maps based on postvaccination hemagglutination inhibition titers against representative H3 variants circulating during the 2015-2016, 2014-2015, and 2012-2013 influenza seasons.
  
  
  RESULTS
  Antigenic maps determined using sera from subjects 18-64 and ≥65 years of age correlated well with each other but poorly with those determined using sera from children. Antigenic maps derived from human postvaccination sera with H1 influenza preexposure also correlated poorly with those derived from sera with neither H1 nor type B influenza preexposure, and the correlation lessened considerably over time. In contrast, antigenic maps derived from human postvaccination sera with only type B influenza preexposure consistently showed good correlation with those derived from sera with neither H1 nor type B influenza preexposure.
  
  
  CONCLUSIONS
  Our results suggest an age-specific difference in human postvaccination responses. Our findings also suggest that prior exposure to H1 or type B influenza may differentially affect cross-reactivity of vaccination-induced H3-specific hemagglutination inhibition antibody responses, and consequently might affect vaccine effectiveness. Our study highlights the need to study the impact of prior exposure on influenza vaccine performance.
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Hang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
authors.forename: Lei
authors.initials: L
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Yangqing
authors.initials: Y
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Courtney L
authors.initials: CL
authors.lastname: Finch
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Martina
authors.initials: M
authors.lastname: Kosikova
authors.affiliation: Laboratory of Respiratory Viral Diseases, Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland.
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, US Food and Drug Administration, Silver Spring, Maryland.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, Mississippi.
authors.forename: Xiu-Feng
authors.initials: XF
authors.lastname: Wan
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D008297:Male; D008875:Middle Aged; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: H3N2 antibody cross-reactivity; Seasonal influenza vaccine; antigenic map; prior exposure; vaccine strain selection