Primary immunization of infants and toddlers in Thailand with Japanese encephalitis chimeric virus vaccine in comparison with SA14-14-2: a randomized study of immunogenicity and safety

Pediatr Infect Dis J. 2014 Jun;33(6):643-9. doi: 10.1097/INF.0000000000000276.

Abstract

Background: The live, attenuated Japanese encephalitis (JE) chimeric virus vaccine (JE-CV) is licensed in Thailand and Australia for prophylaxis of JE in individuals at the age of 12 months. JE-CV has not yet been compared with the SA14-14-2 JE vaccine, which is also licensed in Thailand.

Methods: In this phase 3, observer-blinded trial, 300 children at the age of 9-18 months were randomized 1:1 to receive 1 dose of JE-CV or SA14-14-2. JE neutralizing antibody titers were assessed using PRNT50. The primary endpoint was the noninferiority of seroconversion against JE on Day 28 after JE-CV compared with SA14-14-2, as assessed using the 95% confidence interval of the difference between the groups. Safety and reactogenicity were described in each group using conventional methods, including the reporting of solicited and unsolicited adverse events.

Results: The seroconversion rate on Day 28 was 99.2% in each group. Noninferiority was demonstrated as the difference between the JE-CV and SA14-14-2 groups was -0.012 percentage points (95% confidence interval: -3.6 to 3.6), which was above the required -10%. The seroprotection rate remained very high at Month 6 and comparable between groups, but a slight decrease was observed in the JE-CV group between Months 6 and 12. Current recommendations for both vaccines call for a booster dose 12-24 months after primary immunization to maintain high seroprotection rates in the long term. Geometric mean titers (GMTs) on Day 28 after vaccination were 507 (1/dil) in the JE-CV group and 370 (1/dil) in the SA14-14-2 group, decreasing by 4.3-fold and 3.6-fold, respectively, to Month 6 before remaining stable to Month 12 and comparable between groups. Solicited reactions were all reported at lower rates after vaccination with JE-CV compared with SA14-14-2.

Conclusions: A single dose of JE-CV elicited a noninferior immune response compared with SA14-14-2 and had a satisfactory safety profile.

Trial registration: ClinicalTrials.gov NCT01092507.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antibodies, Viral / blood
  • Child
  • Child, Preschool
  • Encephalitis, Japanese / epidemiology
  • Encephalitis, Japanese / prevention & control*
  • Female
  • Humans
  • Infant
  • Japanese Encephalitis Vaccines / administration & dosage*
  • Japanese Encephalitis Vaccines / adverse effects
  • Japanese Encephalitis Vaccines / immunology
  • Male
  • Thailand / epidemiology

Substances

  • Antibodies, Viral
  • Japanese Encephalitis Vaccines

Associated data

  • ClinicalTrials.gov/NCT01092507