title: Superior antigen-specific CD4+ T-cell response with AS03-adjuvantation of a trivalent influenza vaccine in a randomised trial of adults aged 65 and older.
abstract: BACKGROUND
  The effectiveness of trivalent influenza vaccines may be reduced in older versus younger adults because of age-related immunosenescence. The use of an adjuvant in such a vaccine is one strategy that may combat immunosenescence, potentially by bolstering T-cell mediated responses.
  
  
  METHODS
  This observer-blind study, conducted in the United States (US) and Spain during the 2008-2009 influenza season, evaluated the effect of Adjuvant System AS03 on specific T-cell responses to a seasonal trivalent influenza vaccine (TIV) in ≥65 year-old adults.Medically-stable adults aged ≥65 years were randomly allocated to receive a single dose of AS03-adjuvanted TIV (TIV/AS03) or TIV. Healthy adults aged 18-40 years received only TIV. Blood samples were collected on Day 0, Day 21, Day 42 and Day 180. Influenza-specific CD4+ T cells, defined by the induction of the immune markers CD40L, IL-2, IFN-γ, or TNF-α, were measured in ex vivo cultures of antigen-stimulated peripheral blood mononuclear cells.
  
  
  RESULTS
  A total of 192 adults were vaccinated: sixty nine and seventy three ≥65 year olds received TIV/AS03 and TIV, respectively; and fifty 18 - 40 year olds received TIV. In the ≥65 year-old group on Day 21, the frequency of CD4+ T cells specific to the three vaccine strains was superior in the TIV/AS03 recipients to the frequency in TIV (p < 0.001). On Days 42 and 180, the adjusted-geometric mean specific CD4+ T-cell frequencies were also higher in the TIV/AS03 recipients than in the TIV recipients (p < 0.001). Furthermore, the adjusted-geometric mean specific CD4+ T-cell frequencies were higher in the ≥65 year-old recipients of TIV/AS03 than in the18 - 40 year old recipients of TIV on Days 21 (p = 0.006) and 42 (p = 0.011).
  
  
  CONCLUSIONS
  This positive effect of AS03 Adjuvant System on the CD4+ T-cell response to influenza vaccine strains in older adults could confer benefit in protection against clinical influenza disease in this population.
  
  
  BACKGROUND
  (Clinicaltrials.gov.). NCT00765076.
authors: Robert B
authors: RB
authors: Couch
authors: José M
authors: JM
authors: Bayas
authors: Covadonga
authors: C
authors: Caso
authors: Department of Molecular Virology and Microbiology, Baylor College of medicine, Houston, Texas, USA. mbawuikein@yahoo.com.
authors: Innocent Nnadi
authors: IN
authors: Mbawuike
authors: Concepción Núñez
authors: CN
authors: López
authors: Carine
authors: C
authors: Claeys
authors: Mohamed
authors: M
authors: El Idrissi
authors: Caroline
authors: C
authors: Hervé
authors: Béatrice
authors: B
authors: Laupèze
authors: Lidia
authors: L
authors: Oostvogels
authors: Philippe
authors: P
authors: Moris
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000293:Adolescent; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D005260:Female; D006801:Humans; D007252:Influenza Vaccines / Q000145:classification / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D008297:Male; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines