title: Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults.
abstract: BACKGROUND
  An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone(®) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety.
  
  
  METHODS
  This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the 2012-2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination.
  
  
  RESULTS
  1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction.
  
  
  CONCLUSIONS
  Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines.
authors.affiliation: Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, 1100 S. Grand Boulevard, St. Louis, MO 63104, USA. Electronic address: gorsegj@slu.edu.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Gorse
authors.affiliation: University of Rochester School of Medicine, Rochester General Hospital, Rochester, NY 14621, USA. Electronic address: ann.falsey@rochestergeneral.org.
authors.forename: Ann R
authors.initials: AR
authors.lastname: Falsey
authors.affiliation: Sanofi Pasteur, Inc., 1 Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: ayca.ozol-godfrey@sanofipasteur.com.
authors.forename: Ayca
authors.initials: A
authors.lastname: Ozol-Godfrey
authors.affiliation: Sanofi Pasteur, Inc., 1 Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: victoria.landolfi@sanofipasteur.com.
authors.forename: Victoria
authors.initials: V
authors.lastname: Landolfi
authors.affiliation: Sanofi Pasteur, Inc., 1 Discovery Drive, Swiftwater, PA 18370, USA. Electronic address: peter.tsang@sanofipasteur.com.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Tsang
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D014481:United States; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: Adults; ClinicalTrials.gov no. NCT01712984; Immunogenicity; Intradermal; Phase III; Quadrivalent influenza vaccine; Safety