title: A dose-ranging study in older adults to compare the safety and immunogenicity profiles of MF59®-adjuvanted and non-adjuvanted seasonal influenza vaccines following intradermal and intramuscular administration.
abstract: Strategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged ≥65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 µg of A/H1N1 and B, differing in A/H3N2 content (6 µg or 12 µg), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 µg of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 µg or 30 µg) and/or in MF59(®) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P<0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P<0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery.
  
  
  BACKGROUND
  http://www.clinicaltrials.gov: NCT00848848.
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Della Cioppa
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Uwe
authors.initials: U
authors.lastname: Nicolay
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Lindert
authors.affiliation: Centre for Vaccinology; CEVAC; Ghent University and University Hospital; Belgium.
authors.forename: Geert
authors.initials: G
authors.lastname: Leroux-Roels
authors.affiliation: Centre for Vaccinology; CEVAC; Ghent University and University Hospital; Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Clement
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Galli
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Nicola
authors.initials: N
authors.lastname: Groth
authors.affiliation: NanoPass Technologies; Nes Ziona, Israel.
authors.forename: Yotam
authors.initials: Y
authors.lastname: Levin
authors.affiliation: Novartis Vaccines; Cambridge, MA USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D004306:Dose-Response Relationship, Immunologic; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage / Q000009:adverse effects*; D013185:Squalene / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000276:Adjuvants, Immunologic; D007252:Influenza Vaccines; C089950:MF59 oil emulsion; D011136:Polysorbates; D013185:Squalene
keywords: MF59; adjuvant; influenza; intradermal; seasonal; vaccine
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