Safety and immunogenicity of a novel human Enterovirus 71 (EV71) vaccine: A randomized, placebo-controlled, double-blind, Phase I clinical trial

There is an urgent need for a novel vaccine that is effective against human Enterovirus 71 (EV71) outbreaks. A double-blind, randomized controlled study was to evaluate the safety and immunogenicity of a human EV71 vaccine in healthy adults, children and infants. The vaccine dosages were 200 U and 400 U for children and adults, and 100 U, 200 U and 400 U for infants. Subjects were randomized to receive different dosages of the vaccine or placebo. Adults received intramuscular injection on Days 0, 14 and 28. Children and Infants received on Days 0, 28 and 56. The novel human EV71 inactivated vaccine was well tolerated and highly immunogenic in healthy volunteers, especially in infant populations. For immune response, the seropositive rates (with titers ≥≥1:8) of neutralizing antibody [NTAb] increased to 100% for all dosage groups after the second vaccination. For NTAb seronegative infants before vaccination, after one dose, the NTAb GMTs were 29.7 (95% CI, 13.1–67.2), 10.1 (95% CI, 6.6–15.3), and 27.4 (95% CI, 14.3–52.2) in the 100 U, 200 U, and 400 U vaccine groups, respectively; after two doses, the GMTs were 114.1 (95% CI, 44.5–292.4), 159.5 (95% CI, 49.3–515.3), and 509.0 (95% CI, 181.3–1429.1), respectively.Trial registration: ClinicalTrial.gov identifier: NCT01273246 and NCT01273233.

► HFMD outbreaks cause high mortality in mainland China since 2008. ► Enterovirus 71 (EV71) was associated with high-mortality HFMD outbreaks. ► EV71 vaccine will be the most effective measure to reduce morbidity and mortality. ► The Phase I clinical study evaluated safety and immunogenicity of EV71 vaccine. ► EV71 was well tolerated and highly immunogenic in healthy subjects.