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. Issue 15 (6th April 2023)

• Record Type: Journal Article
• Authors: Sanchez, Leilani; Nakama, Takahiro; Nagai, Hideaki; Matsuoka, Osamu; Inoue, Satoshi; Inoue, Takahiro; Shrestha, Anju; Pandey, Aseem; Chang, Lee-Jah; De Bruijn, Iris
• Is Part Of: Vaccine. Volume 41:Issue 15(2023)
• Page Start: 2553
• Page End: 2561
• Publication Date: 2023-04-06
• Subjects: Immunogenicity -- Safety -- High-dose quadrivalent influenza vaccine -- Older adults -- Clinical study -- Japan; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2023.02.071
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Standard-dose (IIV4-SD) influenza vaccine offer limited protection in older adults. High-dose vaccine (IIV4-HD), licensed in 33 countries offer better protection. Intramuscular IIV4-HD was superior vs subcutaneous IIV4-SD in older adults in Japan. IIV4-HD vaccine was well-tolerated in the study population. 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 ).