Immunogenicity and safety of an inactivated enterovirus 71 vaccine administered simultaneously with recombinant hepatitis B vaccine and group A meningococcal polysaccharide vaccine: a phase IV, open-label, single-center, randomized, non-inferiority trial.

BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of the combined EV71 vaccine with recombinant hepatitis B vaccine (HepB) and group A meningococcal polysaccharide vaccine (MenA) is not inferior to separate administration of each vaccine.

METHODS: The study was designed as a randomized, open-label, and non-inferiority trial, and was registered at ClinicalTrials.gov (NCT03274102). A total of 775 healthy infants aged 6 months were randomized 1:1:1 to simultaneous administration (SI) or separate administration (SE1:EV71 and SE2: HepB followed by MenA).

RESULTS: According to per protocol set, antibody response against EV71, hepatitis B virus and group A meningococcal polysaccharide was similar regardless of administration schedule. With the non-inferiority margin set at 10%, the seroconversion of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) was not inferior to that of SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72]). The occurrences of adverse reactions of each vaccination regimen were comparable (60.62% vs 52.33% and 56.98%, P = 0.16).

CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA shows non inferiority in immunogenicity and safety compared with separate administration.

CLINICAL TRIAL REGISTRATION: NCT03274102.