Immunogenicity and safety of the quadrivalent inactivated split-virion influenza vaccine in populations aged ≥ 3 years: A phase 3, randomized, double-blind, non-inferiority clinical trial.

This study aimed to evaluate the immunogenicity non-inferiority and safety of the quadrivalent inactivated split-virion influenza vaccine in participants ≥ 3 years old. A total of 3,328 participants were enrolled. Participants 3-8 years old were administered one or two doses of the investigational vaccine or one dose of the control vaccine, whereas the other participants were administered only one dose of the investigational or control vaccine. The immunogenicity and occurrence of adverse events (AEs) after 30 days of full-course vaccination and serious adverse events (SAEs) within 6 months after full-course vaccination were assessed. The sero-conversion rates (SCRs) of anti-H1N1, H3N2, B(Y), and B(V) antibodies in the test group were 74.64%, 87.40%, 82.66%, and 78.89%, respectively, and their geometric mean titers were 1:250.13, 1:394.54, 1:200.84, and 1:94.91, respectively, which were non-inferior to those in the control group. The SCRs and sero-protection rates in the two-dose group of participants 3-8 years old were greater than those in the one-dose group. The incidences of total AEs and adverse reactions in the test group were 31.6% and 21.7%, respectively, which were close to those in the control group. In the two-dose group, the incidence of adverse reactions was considerably lower in the second dose (5.5%) than in the first dose (14.7%). Most AEs were grade 1 in severity, and no SAEs were recorded. The investigational vaccine had immunogenicity non-inferior to the control vaccine, and two doses were more effective than one dose in participants 3-8 years old, with a good overall safety.Trial registration: CTR20200715.

People in China are frequently infected by influenza viruses in specific seasons, causing a large burden of disease. Influenza viruses have distinct phenotypes depending on the season. Therefore, vaccines that can effectively prevent the infection of various influenza virus phenotypes need to be developed. The quadrivalent inactivated split-virion influenza vaccine is effective against four influenza virus phenotypes. In this trial, the immunogenicity and safety of the quadrivalent inactivated split-virion influenza vaccine (investigational vaccine) developed by Dalian Aleph Biomedical Co., Ltd. were evaluated. A total of 3,328 participants ≥ 3 years old were included. Participants 3­8 years old were further divided based on the presence or absence of a history of influenza vaccination. Those participants without a vaccination history were administered one or two doses of the investigational vaccine or one dose of a marketed quadrivalent influenza vaccine (control vaccine), and those participants with a vaccination history were administered one dose of the investigational or control vaccine. This study showed for the first time that the immunogenicity and safety of the investigational vaccine were not inferior to those of the control vaccine and that the two-dose procedure induced a good immune effect in the 3­8-year-old group. In conclusion, administration of the investigational vaccine can prevent seasonal influenza in populations aged ≥ 3 years.