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

Vaccine. 2023 Apr 6;41(15):2553-2561. doi: 10.1016/j.vaccine.2023.02.071. Epub 2023 Mar 10.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Viral
  • Double-Blind Method
  • East Asian People
  • Hemagglutination Inhibition Tests
  • Humans
  • Immunogenicity, Vaccine*
  • Influenza Vaccines* / immunology
  • Influenza, Human* / prevention & control
  • Middle Aged
  • Vaccines, Combined
  • Vaccines, Inactivated

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Combined
  • Vaccines, Inactivated

Associated data

  • ClinicalTrials.gov/NCT04498832