title: Difference in immune response in vaccinated and unvaccinated Swedish individuals after the 2009 influenza pandemic.
abstract: BACKGROUND
  Previous exposures to flu and subsequent immune responses may impact on 2009/2010 pandemic flu vaccine responses and clinical symptoms upon infection with the 2009 pandemic H1N1 influenza strain. Qualitative and quantitative differences in humoral and cellular immune responses associated with the flu vaccination in 2009/2010 (pandemic H1N1 vaccine) and natural infection have not yet been described in detail. We designed a longitudinal study to examine influenza- (flu-) specific immune responses and the association between pre-existing flu responses, symptoms of influenza-like illness (ILI), impact of pandemic flu infection, and pandemic flu vaccination in a cohort of 2,040 individuals in Sweden in 2009-2010.
  
  
  METHODS
  Cellular flu-specific immune responses were assessed by whole-blood antigen stimulation assay, and humoral responses by a single radial hemolysis test.
  
  
  RESULTS
  Previous seasonal flu vaccination was associated with significantly lower flu-specific IFN-γ responses (using a whole-blood assay) at study entry. Pandemic flu vaccination induced long-lived T-cell responses (measured by IFN-γ production) to influenza A strains, influenza B strains, and the matrix (M1) antigen. In contrast, individuals with pandemic flu infection (PCR positive) exhibited increased flu-specific T-cell responses shortly after onset of ILI symptoms but the immune response decreased after the flu season (spring 2010). We identified non-pandemic-flu vaccinated participants without ILI symptoms who showed an IFN-γ production profile similar to pandemic-flu infected participants, suggesting exposure without experiencing clinical symptoms.
  
  
  CONCLUSIONS
  Strong and long-lived flu-M1 specific immune responses, defined by IFN-γ production, in individuals after vaccination suggest that M1-responses may contribute to protective cellular immune responses. Silent flu infections appeared to be frequent in 2009/2010. The pandemic flu vaccine induced qualitatively and quantitatively different humoral and cellular immune responses as compared to infection with the 2009 H1N1 pandemic H1N1 influenza strain.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Magalhaes
authors.forename: Mikael
authors.initials: M
authors.lastname: Eriksson
authors.forename: Charlotte
authors.initials: C
authors.lastname: Linde
authors.forename: Rashid
authors.initials: R
authors.lastname: Muhammad
authors.forename: Lalit
authors.initials: L
authors.lastname: Rane
authors.forename: Aditya
authors.initials: A
authors.lastname: Ambati
authors.forename: Rebecca
authors.initials: R
authors.lastname: Axelsson-Robertson
authors.forename: Bahareh
authors.initials: B
authors.lastname: Khalaj
authors.forename: Nancy
authors.initials: N
authors.lastname: Alvarez-Corrales
authors.forename: Giulia
authors.initials: G
authors.lastname: Lapini
authors.forename: Emanuele
authors.initials: E
authors.lastname: Montomoli
authors.forename: Annika
authors.initials: A
authors.lastname: Linde
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.affiliation: Center for allogeneic stem cell transplantation, Karolinska University Hospital, Stockholm, Sweden. markus.maeurer@ki.se.
authors.forename: Markus
authors.initials: M
authors.lastname: Maeurer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013548:Sweden / Q000453:epidemiology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007371:Interferon-gamma