Immunogenicity and safety of an inactivated COVID-19 vaccine (CoronaVac®) co-administered with an inactivated enterovirus type 71 vaccine (Inlive®): A phase 4, randomized, controlled trial

This study aimed to provide evidence for co-administration of the COVID-19 and EV71 vaccines in children aged 3 to 5 years. We conducted a phase 4, open-label, randomized, and controlled study. A total of 520 children were randomly allocated to two groups: Group C received the COVID-19 and EV71 vaccines simultaneously, while Group N received the two vaccines separately. The primary immunogenicity endpoints were the seroconversion rates of anti-SARS-CoV-2 and anti-EV71 antibodies 28 days after the second dose of each respective vaccine. Before vaccination, none of the participants was seropositive for anti-SARS-CoV-2 antibodies, and the baseline seropositivity for anti-EV71 antibodies was low (Group C: 14.86%; Group N: 17.83%). After completing full vaccination, the seroconversion rate of anti-SARS-CoV-2 antibodies reached 100% in both groups, while for anti-EV71 antibodies, the seroconversion rates were 97.99% in Group C and 98.70% in Group N. The lower limit of the 95% confidence interval for the difference in seroconversion rates between the two groups for both COVID-19 and EV71 vaccines met the predefined non-inferiority criteria. Six months post-vaccination, the antibody levels remained high for both vaccines, with the seropositive rates of anti-SARS-CoV-2 antibodies at 91.21% in Group C and 92.77% in Group N, and the seropositive rates of anti-EV71 antibodies at 99.16% in Group C and 99.15% in Group N. Safety analysis revealed a lower incidence of adverse reactions in Group C compared to Group N (28.85% vs 45.56%), primarily solicited. Co-administration of the COVID-19 and EV71 vaccines demonstrated a positive safety profile and non-inferior immune responses. Trial registration NumberNCT04993365 (ClinicalTrials.gov).