title: Longevity and determinants of protective humoral immunity after pandemic influenza infection.
abstract: BACKGROUND
  Antibodies to influenza hemagglutinin are the primary correlate of protection against infection. The strength and persistence of this immune response influences viral evolution and consequently the nature of influenza epidemics. However, the durability and immune determinants of induction of humoral immunity after primary influenza infection remain unclear.
  
  
  OBJECTIVE
  The spread of a novel H1N1 (A[H1N1]pdm09) virus in 2009 through an unexposed population offered a natural experiment to assess the nature and longevity of humoral immunity after a single primary influenza infection.
  
  
  METHODS
  We followed A(H1N1)pdm09-seronegative adults through two influenza seasons (2009-2011) as they developed A(H1N1)pdm09 influenza infection or were vaccinated. Antibodies to A(H1N1)pdm09 virus were measured by hemagglutination-inhibition assay in individuals with paired serum samples collected preinfection and postinfection or vaccination to assess durability of humoral immunity. Preexisting A(H1N1)pdm09-specific multicytokine-secreting CD4 and CD8 T cells were quantified by multiparameter flow cytometry to test the hypothesis that higher frequencies of CD4(+) T-cell responses predict stronger antibody induction after infection or vaccination.
  
  
  RESULTS
  Antibodies induced by natural infection persisted at constant high titer for a minimum of approximately 15 months. Contrary to our initial hypothesis, the fold increase in A(H1N1)pdm09-specific antibody titer after infection was inversely correlated to the frequency of preexisting circulating A(H1N1)pdm09-specific CD4(+)IL-2(+)IFN-γ(-)TNF-α(-) T cells (r = -0.4122; P = 0.03).
  
  
  CONCLUSIONS
  The longevity of protective humoral immunity after influenza infection has important implications for influenza transmission dynamics and vaccination policy, and identification of its predictive cellular immune correlate could guide vaccine development and evaluation.
authors.affiliation: 1 Section of Respiratory Infections, National Heart and Lung Institute, and.
authors.forename: Saranya
authors.initials: S
authors.lastname: Sridhar
authors.forename: Shaima
authors.initials: S
authors.lastname: Begom
authors.forename: Katja
authors.initials: K
authors.lastname: Hoschler
authors.forename: Alison
authors.initials: A
authors.lastname: Bermingham
authors.forename: Walt
authors.initials: W
authors.lastname: Adamson
authors.forename: William
authors.initials: W
authors.lastname: Carman
authors.forename: Steven
authors.initials: S
authors.lastname: Riley
authors.forename: Ajit
authors.initials: A
authors.lastname: Lalvani
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage; D007251:Influenza, Human / Q000097:blood / Q000453:epidemiology* / Q000276:immunology* / Q000517:prevention & control; D058873:Pandemics; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D007252:Influenza Vaccines
keywords: T cells; antibodies; epidemiology; immunology; pandemic influenza