title: Dissecting the immune response to MF59-adjuvanted and nonadjuvanted seasonal influenza vaccines in children less than three years of age.
abstract: BACKGROUND
  Annual seasonal influenza epidemics are particularly dangerous for the very young, the elderly and chronically ill individuals, in whom infection can cause severe morbidity, hospitalization and death. Existing, nonadjuvanted influenza vaccines exhibit a suboptimal immunogenicity and efficacy in immunologically naive subjects such as young children.
  
  
  METHODS
  This phase II, randomized clinical trial was conducted to evaluate the antibody and cell-mediated responses to a trivalent influenza vaccine administered without adjuvant (TIV) or adjuvanted with MF59 (ATIV) in previously nonvaccinated children less than 3 years of age.
  
  
  RESULTS
  The MF59-adjuvanted vaccine was well tolerated, and induced higher titers of hemagglutination inhibition antibodies able to recognize strains different from the one used in the vaccine (heterovariant) than TIV. The presence of the adjuvant MF59 induced a larger expansion of vaccine-specific CD4 T cells. Interestingly, the adjuvant MF59 did not modify the cytokine profile of the elicited T cells, characterized by the production of IL-2 and TNF-α, and did not bias the response toward either Th1 or Th2. The advantage of ATIV over TIV was more pronounced for the virus strains that had not circulated in the years that preceded this study and for the heterovariant strains.
  
  
  CONCLUSIONS
  These data highlight the relevant role played by the oil-in-water adjuvant MF59 in enhancing the immunogenicity of inactivated influenza vaccines in immunologically naive individuals.
authors.affiliation: From the *Novartis Vaccines, Siena, Italy and Cambridge, MA; †Sint Vincentius Ziekenhuis, Antwerp, Belgium; ‡Kinderartsenassociatie, Hasselt, Belgium; §ImmuneHealth, Charleroi, Belgium; and ¶Institute for Medical Immunology, Université Libre de Bruxelles, Charleroi, Belgium.
authors.forename: Luisanna
authors.initials: L
authors.lastname: Zedda
authors.forename: Eduardo
authors.initials: E
authors.lastname: Forleo-Neto
authors.forename: André
authors.initials: A
authors.lastname: Vertruyen
authors.forename: Marc
authors.initials: M
authors.lastname: Raes
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marchant
authors.forename: Wim
authors.initials: W
authors.lastname: Jansen
authors.forename: Heather
authors.initials: H
authors.lastname: Clouting
authors.forename: Ashwani
authors.initials: A
authors.lastname: Arora
authors.forename: Mark E
authors.initials: ME
authors.lastname: Beatty
authors.forename: Grazia
authors.initials: G
authors.lastname: Galli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007223:Infant; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D007376:Interleukin-2; C089950:MF59 oil emulsion; D011136:Polysorbates; D014409:Tumor Necrosis Factor-alpha; D013185:Squalene