Long-Term Immunogenicity Study of an Aluminum Phosphate-Adjuvanted Inactivated Enterovirus A71 Vaccine in Children: An Extension to a Phase 2 Study

Abstract

BackgroundEV-A71 causes hand, foot, and mouth disease with potentially fatal complications such as encephalitis and acue flaccid myelitis in infants and children. This study examined the long-term immunity conferred by EV71vac, an inactivated EV-A71 vaccine based on the B4 subgenotype adjuvanted with aluminum phosphate, in children from the age of > 2 months to < 6 years for up to 5 years after the first immunization.MethodsA total of 227 subjects from age of 2 months to 6 years who had previously received either EV71vac or placebo in the phase 2 clinical study were enrolled. Subjects were split into age groups: 2 years to < 6 years (Group 2b), 6 months to < 2 years (Group 2c), and 2 months to < 6 months (Group 2d). Serum samples were taken periodically for up to five years after the first dose for immunogenicity against EV-A71.ResultsAt year 5, the neutralizing antibody titers against B4 subgenotype remained high at 621.38 to 978.20, 841.40 to 1159.93, and 477.71 to 745.07 for Groups 2b, 2c, and 2d, respectively. Cross-neutralizing titers at year 5 were 99.14 to 444.30 and 341.94 to 998.20 against B5 and C4a subgenotypes, respectively. Nearly all subjects remained seroprotected at year five (95.8 to 100%). No long-term safety issues were reported.ConclusionThis study shows that using the current dosing regimen, EV71vac conferred persistent immunity against EV-A71 for at least five years after the first vaccination in children from the age of two months to six years.SummaryEV-A71 neutralizing antibody persisted at high level throughout five years post vaccination in children of two months to six years old.