A randomized study of the immunogenicity and safety of Japanese encephalitis chimeric virus vaccine (JE-CV) in comparison with SA14-14-2 vaccine in children in the Republic of Korea

Abstract

A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12-24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14-14-2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14-14-2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14-14-2 was 0.9 percentage points (95% confidence interval [CI]: -2.35; 4.68), which was above the required -10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14-14-2; all children except one (Group SA14-14-2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14-14-2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14-14-2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12-24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers.

Trial registration: ClinicalTrials.gov NCT01396512.

Keywords: AE, adverse event; AESI, AE of Special Interest; AR, adverse reaction; CI, confidence interval; FAS, Full Analysis Set; GMT, Geometric mean titers; GMTRs, GM of titer ratios; JE, Japanese encephalitis; JE-CV, JE chimeric virus vaccine; JEV, JE virus; Japanese encephalitis (JE) vaccine; MBDV, mouse brain derived inactivated anti-JE vaccines; PP, Per Protocol; PRNT50, 50% plaque reduction neutralization test; Phase 3 trial; SAE, serious adverse events.; children; immunogenicity; safety.

Figures

Figure 1.

Disposition of children.1 JE neutralizing antibody titer ≥ 10 (1/dil) in children who were seronegative (titer < 10 [1/dil])at baseline or a ≥ 4-fold rise in JE neutralizing antibody titers in children who were seropositive (titer ≥ 10 [1/dil]) at baseline;2 JE neutralizing antibody titer ≥ 10 (1/dil).