Immunogenicity and safety of high-dose quadrivalent influenza vaccine in Japanese adults ≥65 years of age: a randomized controlled clinical trial.

A trivalent high-dose inactivated influenza vaccine has been licensed in healthy adults ≥65 years of age and provides better protection against influenza infection and related complications than trivalent standard-dose vaccine. This phase I/II clinical trial (NCT03233217), conducted at two sites in Japan, examined the safety and immunogenicity of a quadrivalent formulation of the high-dose inactivated influenza vaccine (IIV4-HD). Healthy adults ≥65 years of age were randomized to receive IIV4-HD by intramuscular injection (n = 60), IIV4-HD by subcutaneous injection (n = 60), or a quadrivalent standard-dose inactivated influenza vaccine (IIV4-SD) by subcutaneous injection (n = 55). Irrespective of administration route, post-vaccination (day 28-35) hemagglutination inhibition geometric mean titers and seroconversion rates were higher for IIV4-HD than for IIV4-SD. Hemagglutination inhibition geometric mean titers and seroconversion rates were also higher for intramuscular than subcutaneous administration of IIV4-HD. Solicited reactions were more common in participants who received IIV4-HD administered subcutaneously than in those who received IIV4-HD administered intramuscularly or IIV4-SD administered subcutaneously. Unsolicited adverse events were similar between the vaccine groups, and no safety signals were detected. This study showed that IIV4-HD administered by either intramuscular or subcutaneous injection was well tolerated and highly immunogenic in healthy Japanese adults ≥65 years of age. Although this study was descriptive, the results add to the evidence that high-dose inactivated influenza vaccines are more immunogenic than standard-dose vaccines in this age group and that intramuscular administration provides greater immunogenicity and lower reactogenicity than subcutaneous administration.