title: GLA-SE, a synthetic toll-like receptor 4 agonist, enhances T-cell responses to influenza vaccine in older adults.
abstract: BACKGROUND
  The decline in influenza vaccine efficacy in older adults is associated with a limited ability of current split-virus vaccines (SVVs) to stimulate cytotoxic T lymphocyte (CTL) responses required for clinical protection against influenza.
  
  
  METHODS
  The Toll-like receptor 4 agonist glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) was combined with SVV to stimulate peripheral blood mononuclear cells (PBMCs) in vitro to determine the cytokine response in dendritic cell subsets. Stimulated PBMCs were then challenged with live influenza virus to mimic the response to natural infection following vaccination, using previously identified T-cell correlates of protection.
  
  
  RESULTS
  GLA-SE significantly increased the proportion of myeloid dendritic cells that produced tumor necrosis factor α, interleukin 6, and interleukin 12. When combined with SVV to stimulate PBMCs in vitro, this effect of GLA-SE was shown to regulate a T-helper 1 cell response upon challenge with live influenza virus; interleukin 10 production was suppressed, thus significantly increasing the interferon γ to interleukin 10 ratio and the cytolytic (granzyme B) response to influenza virus challenge, both of which have been shown to correlate with protection against influenza in older adults.
  
  
  CONCLUSIONS
  Our findings suggest that a novel adjuvant, GLA-SE, combined with standard SVV has the potential to significantly improve vaccine-mediated protection against influenza in older adults.
authors.affiliation: Vancouver Coastal Health Research Institute,Vancouver, Canada.
authors.forename: Hayedeh
authors.initials: H
authors.lastname: Behzad
authors.forename: Anke L W
authors.initials: AL
authors.lastname: Huckriede
authors.forename: Laura
authors.initials: L
authors.lastname: Haynes
authors.forename: Beth
authors.initials: B
authors.lastname: Gentleman
authors.forename: Krysta
authors.initials: K
authors.lastname: Coyle
authors.forename: Jan C
authors.initials: JC
authors.lastname: Wilschut
authors.forename: Tobias R
authors.initials: TR
authors.lastname: Kollmann
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.forename: Janet E
authors.initials: JE
authors.lastname: McElhaney
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007252:Influenza Vaccines / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists*; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; D007252:Influenza Vaccines; D051197:Toll-Like Receptor 4; D022223:Vaccines, Subunit