title: Superior immunogenicity of seasonal influenza vaccines containing full dose of MF59 (®) adjuvant: results from a dose-finding clinical trial in older adults.
abstract: BACKGROUND
  MF59-adjuvanted influenza vaccines have superior immunogenicity in older adults compared with non-adjuvanted vaccines. We assessed whether changing formulation (i.e., increasing H3N2 antigen or decreasing the quantity of adjuvant) of the licensed, MF59-adjuvanted trivalent influenza subunit vaccine Fluad (®) (Novartis Vaccines and Diagnostics) improves the risk-benefit profile in vaccinees aged ≥ 65 years.
  
  
  RESULTS
  A significant dose-response relationship was observed between antibody levels and MF59 dose; full dose formulations elicited the strongest immune responses, meeting immunogenicity licensure criteria by Day 8. Doubling H3N2 antigen content did not increase the response to this antigen. Increased frequency of circulating CD4+ T-cells specific for vaccine antigens were detected by Day 8; magnitude and functional profile of the CD4+ T-cell response was comparable across the different vaccination groups. Mild to moderate solicited local reactions were more common with vaccines formulated with higher doses of MF59 (®) , but there were no MF59- or antigen dose-related increase in the frequency of solicited systemic reactions or unsolicited adverse events and serious adverse events.
  
  
  METHODS
  We report on 357 subjects who received one of eight intramuscular vaccine formulations. Hemagglutination-inhibiting antibodies were assayed on Days 1, 8 and 22; magnitude and functional profile of CD4+ T-cell responses to vaccine antigens were assessed in subsets. Solicited adverse reactions were reported via diary cards for seven days after vaccination and spontaneous adverse events were monitored throughout the study.
  
  
  CONCLUSIONS
  This study confirms that the current formulation is the optimal one for MF59-adjuvanted influenza vaccine for use in older adults.
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge MA, USA. giovanni.della_cioppa@novartis.com
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.forename: Kelly
authors.initials: K
authors.lastname: Lindert
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.forename: Frederic
authors.initials: F
authors.lastname: Clement
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.forename: Grazia
authors.initials: G
authors.lastname: Galli
authors.forename: Nicola
authors.initials: N
authors.lastname: Groth
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000276:Adjuvants, Immunologic; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000517:prevention & control; D007273:Injections, Intramuscular; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D013185:Squalene / Q000008:administration & dosage / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene