title: Humoral and cellular immune responses in children given annual immunization with trivalent inactivated influenza vaccine.
abstract: BACKGROUND
  There have been no prior reports of the frequency of circulating influenza-specific, interferon gamma-producing memory CD4+ and CD8+ T-cells in healthy children who have received multiple influenza immunizations.
  
  
  METHODS
  We evaluated 21 previously immunized children, ages 3 to 9 years, before and 1 month after administration of trivalent inactivated influenza vaccine. Frequencies of influenza-specific CD4+ and CD8+ T-cells stimulated with trivalent inactivated influenza vaccine or A/Panama (H3N2) virus were determined by flow cytometry, and antibody responses to vaccine strains and a drifted H3N2 strain were measured by hemagglutination inhibition assay and neutralizing antibody assays.
  
  
  RESULTS
  Mean change in CD4+ and in CD8+ T-cell frequencies after immunization was 0.01% (P > 0.39) with postimmunization CD4+ frequencies higher than CD8+ frequencies. Children with more previous vaccinations had a higher baseline frequency of CD4+ T-cells (P = 0.0002) but a smaller increase or even a decline from baseline after immunization (P = 0.003). An association between age and change in frequency was not detected. Baseline geometric mean titers (GMTs) and seroprotection rates were significantly higher in older children against A/Panama (neutralizing baseline GMT, P = 0.0488) and A/New Caledonia (hemagglutination inhibition baseline GMT and seroprotection, P < 0.0297). Baseline GMTs against B/Hong Kong were not associated with age or quantity of prior vaccinations.
  
  
  CONCLUSIONS
  These findings suggest that children may plateau in CD4+ T-cell responses to influenza antigens with repeated exposures and that the number of exposures may play a large role in building a memory CD4+ T-cell response to influenza A, perhaps independently from age.
authors.affiliation: Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305-5208, USA.
authors.forename: Alenka M
authors.initials: AM
authors.lastname: Zeman
authors.forename: Tyson H
authors.initials: TH
authors.lastname: Holmes
authors.forename: Shaye
authors.initials: S
authors.lastname: Stamatis
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: He
authors.forename: Nancy
authors.initials: N
authors.lastname: Bouvier
authors.forename: George
authors.initials: G
authors.lastname: Kemble
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
authors.forename: David B
authors.initials: DB
authors.lastname: Lewis
authors.forename: Ann M
authors.initials: AM
authors.lastname: Arvin
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
mesh_terms: D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D018655:Lymphocyte Count; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D009500:Neutralization Tests; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated; D007371:Interferon-gamma