Safety and Immunogenicity of Enterovirus 71 Vaccine (Vero Cell) Administered Simultaneously with Trivalent Split-Virion Influenza Vaccine in Infants Aged 6-7 Months: A Phase 4, Randomized, Controlled Trial

Objective: To assess the immunogenicity and safety of the enterovirus 71 vaccine (Vero cell) (EV71 vaccine) and trivalent split-virion influenza vaccine (IIV3). Methods: Healthy infants aged 6-7 months were recruited from Zhejiang Province, Henan Province, and Guizhou Province and randomly assigned to the simultaneous vaccination group, EV71 group, and IIV3 group at a ratio of 1:1:1. Then, 3 mL blood samples were collected before vaccination and 28 days after the second dose of vaccine. Cytopathic effect inhibition assay was used to detect EV71 neutralization antibody, and cytopathic effect inhibition assay was used to detect influenza virus antibody. Results: A total of 378 infants were enrolled and received the first dose of vaccine and were included in the safety analysis, and 350 infants were involved in the immunogenicity analysis. The adverse events rates were 31.75%, 28.57%, and 34.13% in the simultaneous vaccination group, EV71 group, and IIV3 group (p > 0.05), respectively. No vaccine-related serious adverse events were reported. After two doses of EV71 vaccine, the seroconversion rates of EV71 neutralizing antibody were 98.26% and 97.37% in the simultaneous vaccination group and the EV71 group, respectively. After two doses of IIV3, the simultaneous vaccination group and the IIV3 group, respectively, had seroconversion rates of 80.00% and 86.78% for H1N1 antibody, 99.13% and 98.35% for H3N2 antibody, and 76.52% and 80.99% for B antibody. There was no statistically significant difference in the seroconversion rates of influenza virus antibodies between groups (p > 0.05). Conclusions: The coadministration of EV71 vaccine and IIV3 has good safety and immunogenicity in infants aged 6-7 months.