Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults

Background: An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone (R) 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 (11V4-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 11V4-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 11V3-ID, and 846 with an investigational 11V3-ID. For all four vaccine strains, antibody responses to 11V4-ID were statistically non-inferior to the response to the 11V3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to 11V3-ID lacking the corresponding B strain. Adverse events were similar for 11V4-ID and 11V3-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. 11V4-ID was statistically non-inferior to the two pooled 11V3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. Conclusions: Antibody responses to the 11V4-ID were non-inferior to 11V3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. 11V4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines. (C) 2015 Elsevier Ltd. All rights reserved.