Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults? 60 years of age: Results from a phase III, randomized clinical trial

Background: A high-dose, split-virion inactivated quadrivalent influenza vaccine (IIV4-HD; Sanofi) is being used for the prevention of influenza in multiple countries. This study examined the immunogenic-ity and safety of the IIV4-HD vaccine administered intramuscularly (IM) compared with a locally licensed standard-dose influenza vaccine (IIV4-SD) administered subcutaneously (SC) in Japan. Methods: This was a phase III, randomized, modified double-blind, active-controlled, multi-center study in older adults >= 60 years of age conducted during the Northern Hemisphere (NH) influenza season of 2020-21 in Japan. Participants were randomized in a 1:1 ratio to receive a single IM injection of IIV4-HD or SC injection of IIV4-SD. Hemagglutination inhibition antibody and seroconversion rates were mea-sured at baseline and day 28. Solicited reactions were collected for up to 7 days after vaccination, unso-licited adverse events up to 28 days after vaccination, and serious adverse events throughout the study. Results: The study included 2100 adults >= 60 years of age. IIV4-HD given IM induced superior immune responses versus IIV4-SD given SC as assessed by geometric mean titers for all four influenza strains. Superior seroconversion rates were also observed for IIV4-HD compared to IIV4-SD for all influenza strains. The safety profiles of IIV4-HD and IIV4-SD were similar. IIV4-HD was well tolerated in partici-pants, with no safety concerns identified. Conclusions: IIV4-HD provided superior immunogenicity versus IIV4-SD and was well tolerated in participants >= 60 years of age in Japan. With superior immunogenicity based on the multiple randomized controlled trials and real-world evidence of trivalent high-dose formulation, IIV4-HD is expected to be the first differentiated influenza vaccine in Japan that offer a greater protection against influenza and its complications in adults 60 years of age and older. Study registration: NCT04498832 (clinicaltrials.gov); U1111-1225-1085 (who.int).(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).