Immunogenicity and safety of an inactivated quadrivalent influenza vaccine: A randomized, double-blind, controlled phase III study in healthy population aged ≥3 years.

Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains (H1N1 and H3N2) and one strain from each B lineage (Victoria and Yamagata) may offer broader protection against seasonal influenza. This study examined the immunogenicity and safety of a candidate IIV4. A randomized, double-blind, controlled phase III clinical trial was conducted in healthy subjects aged ≥3 years. Subjects were randomly assigned into three groups in a 2:1:1 ratio, receiving single dose of IIV4 or inactivated trivalent influenza vaccine (IIV3) which contains either B/Victoria strain (BV) or B/Yamagata strain (BY). Blood samples were collected before and 28 days after vaccination to test hemagglutination inhibition (HI) antibodies of the four influenza strains. Safety information was collected for 28 days after vaccination. A total of 2320 subjects (IIV4: 1160, IIV3-BV: 580, IIV3-BY: 580) were enrolled in this study. After vaccination, the seroconversion rates of IIV4 against H1N1, H3N2, BV and BY strains were 77.15%, 81.93%, 60.14% and 64.57%, respectively. Geometric mean titers (GMTs) against the four influenza strains were 523.91, 274.13, 115.35 and 257.81, respectively. The investigational IIV4 was non-inferiority to IIV3 for the four strains, meanwhile superior to IIV3 for additional B strains (B/BV, B/BY). For safety, there had no significant difference in the incidence of the adverse reactions among the three groups (P = 0.5986). No serious adverse events related to vaccination occurred. The IIV4 had good immunogenicity and safety, which added an influenza B protection with no increased safety concerns. (ClinicalTrials.gov number: NCT03853993).