In healthy individuals of 65 years of age, a trivalent high-dose inactivated influenza vaccine has been approved, and it provides greater protection against influenza infection and associated consequences than a trivalent standard-dose vaccination. The safety and immunogenicity of a quadrivalent formulation of the high-dose inactivated influenza vaccine (NCT03233217) were investigated in this phase I/II clinical study (NCT03233217), which was conducted at two locations in Japan (IIV4-HD). Healthy individuals 65 years old were randomly assigned to receive IIV4-HD intramuscularly, IIV4-HD subcutaneously, or a quadrivalent standard-dose inactivated influenza vaccination (IIV4-SD) subcutaneously. IIV4-HD had greater post-vaccination hemagglutination inhibition geometric mean titers and seroconversion rates than IIV4-SD, regardless of delivery method. Hemagglutination inhibition geometric mean titers and seroconversion rates were similarly greater when IIV4-HD was administered intramuscularly rather than subcutaneously. Solicited responses were more prevalent in those who received IIV4-HD subcutaneously vs those who got IIV4-HD intramuscularly or IIV4-SD subcutaneously. Unwanted side events were comparable among vaccination groups, and no safety flags were found.

This study found that IIV4-HD given intramuscularly or subcutaneously was well tolerated and significantly immunogenic in 65-year-old healthy Japanese people. Although this was a descriptive research, the findings add to the evidence that high-dose inactivated influenza vaccinations are more immunogenic than standard-dose vaccines in this age range, and that intramuscular injection is more immunogenic and less reactogenic than subcutaneous administration.