title: MF59 emulsion is an effective delivery system for a synthetic TLR4 agonist (E6020).
abstract: OBJECTIVE
  The effectiveness of vaccines depends on the age and immunocompetence of the vaccinee. Conventional non-adjuvanted influenza vaccines are suboptimal in the elderly and vaccines with improved ability to prevent influenza are required. The TLR4 agonist E6020, either given alone or co-delivered with MF59, was evaluated and compared to MF59 and the TLR9 agonist CpG. Its ability to enhance antibody titres and to modulate the quality of the immune response to a subunit influenza vaccine was investigated.
  
  
  METHODS
  Mice were immunized with either antigens alone, with MF59 or with the TLR agonists alone, or with a combination thereof. Serum samples were assayed for IgG antibody titres and hemagglutination inhibition (HI) titres. Th1/Th2 type responses were determined by titrating IgG subclasses in serum samples and by T-cell cytokine responses in splenocytes.
  
  
  RESULTS
  MF59 was the best single adjuvant inducing HI and T-cell responses in comparison to all alternatives. The co-delivery of E6020 or CpG with MF59 did not further increase antibody titres however shifted towards a more Th1 based immune response.
  
  
  CONCLUSIONS
  Combining adjuvants like E6020 and MF59 allowed a finer tuning of the immune response towards a particular Th bias, thus have significant implications for the development of improved influenza vaccines.
authors.affiliation: Novartis Vaccines, Via Fiorentina 1, Siena, Italy. barbara.baudner@novartis.com
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Baudner
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ronconi
authors.forename: Daniele
authors.initials: D
authors.lastname: Casini
authors.forename: Marco
authors.initials: M
authors.lastname: Tortoli
authors.forename: Jina
authors.initials: J
authors.lastname: Kazzaz
authors.forename: Manmohan
authors.initials: M
authors.lastname: Singh
authors.forename: Lynn D
authors.initials: LD
authors.lastname: Hawkins
authors.forename: Andreas
authors.initials: A
authors.lastname: Wack
authors.forename: Derek T
authors.initials: DT
authors.lastname: O'Hagan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D006385:Hemagglutination Inhibition Tests; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011136:Polysorbates / Q000008:administration & dosage*; D013185:Squalene / Q000008:administration & dosage* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000819:agonists*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D051197:Toll-Like Receptor 4; D013185:Squalene