Immunological non-inferiority and safety of a quadrivalent inactivated influenza vaccine versus two trivalent inactivated influenza vaccines in China: Results from two studies

A quadrivalent, split-virion influenza vaccine (Shz QIV), containing two influenza A strains, and both B lineages strains, has been developed in China. We report the safety and immunogenicity of Shz QIV in two studies: a single-center, phase I, open-label, safety trial (n = 101) and a multicenter, phase III, observer-blind, randomized, safety and immunogenicity trial (n = 7,106) comparing Shz QIV with two trivalent influenza vaccines (Shz TIVs; one containing a B/Victoria-like strain and the other a B/Yamagata-like strain). Participants received one dose of Shz QIV (0.5 mL), except children aged 6 months to 8 years who received one or two doses (0.25 mL or 0.5 mL) depending on previous influenza vaccination. The Shz TIV groups received one or two (0.25 mL) doses depending on previous influenza vaccination (ages 6-35 months) or a single (0.5 mL) dose (ages >= 3 years). Immunogenicity was assessed at baseline and 28 days after the last dose, with safety assessed through to 6 months. The primary objective was to demonstrate the non-inferiority of antibody responses to Shz QIV (0.25 mL and 0.5 mL) versus Shz TIVs for each strain in ages 6-35 months and >= 3 years. Overall, Shz QIV was well tolerated, and showed similar safety to the Shz TIVs. Shz QIV (0.5 mL) induced non-inferior antibody responses to all antigens versus Shz TIV, with superiority demonstrated to the non-corresponding B strain in each TIV. Shz QIV (0.25 mL) non-inferiority in those aged 6-35 months was demonstrated for both A strains and the B/Yamagata-like strain, but not the B/Victoria-like strain. In summary, Shz QIV (0.5 mL) is immunogenic and has a good safety profile. WHO Universal Trial Numbers (UTNs) U1111-1174-4615 and U1111-1174-4698 ClinicalTrials.gov NCT04210349 and NCT03430089

Automated summary

The safety and immunogenicity of the quadrivalent, split-virion influenza vaccine (Shz QIV) developed in China were assessed. The vaccine showed good tolerability and induced immune responses in different age groups, demonstrating non-inferiority against various strains of influenza virus.