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

Abstract

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 immunogenicity 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 measured at baseline and day 28. Solicited reactions were collected for up to 7 days after vaccination, unsolicited 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 participants, 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).

Keywords: Clinical study; High-dose quadrivalent influenza vaccine; Immunogenicity; Japan; Older adults; Safety.

Conflict of interest statement

Declaration of Competing Interest Leilani Sanchez, Aseem Pandey, and Iris De Bruijn are employees of Sanofi and as such may be eligible for stock and stock options. Anju Shrestha was employed with Sanofi when the study was being conducted. Her current affiliation is Regeneron Pharmaceuticals, Inc., Basking Ridge, NJ, USA.Takahiro Nakama was employed with Sanofi when the study was being conducted. His current affiliation is Janssen Pharmaceutical K.K., Tokyo, Japan. Hideaki Nagai received speaker fees from GSK, MSD, and Shionogi. Osamu Matsuoka and Satoshi Inoue have nothing to disclose and report no conflicting interest.Takahiro Inoue was employed with Sanofi when the study was being conducted. His current affiliation is Astellas Pharma, Tokyo, Japan. Lee-Jah Chang was employed with Sanofi when the study was being conducted. His current affiliation is AstraZeneca, Gaithersburg, MD, USA.

Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.