Long-term follow-up of Japanese encephalitis chimeric virus vaccine: Immune responses in children

Vaccine. 2016 Nov 4;34(46):5664-5669. doi: 10.1016/j.vaccine.2016.09.018. Epub 2016 Sep 27.

Abstract

Background: A single dose of live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) was shown to be immunogenic and well tolerated when given either as a booster to formalin-inactivated Japanese encephalitis (JE)-vaccine (mouse brain-derived vaccine [MBDV])-primed 2-5-year-olds, or as a primary vaccination to JE-vaccine-naïve 12-24-month-old toddlers in Thailand. A 5-year follow-up assessment of immune response persistence over time was conducted.

Methods: Four additional visits (at 2, 3, 4, and 5years) for immunologic assessments were added to the original 12-month open-label crossover study, in which 100 healthy children aged 2-5years with a history of two-dose primary vaccination with MBDV (according to the Thai Expanded Program for Immunization schedule), and 200 healthy JE-vaccine-naïve 12-24-month-old toddlers, were randomized 1:1 to receive JE-CV, containing ⩾4 log10 plaque forming units, 1month before or after hepatitis A control vaccine.

Results: In MBDV-primed 2-5-year-olds (n=78), the immune response to the JE-CV vaccine persisted up to at least 5years after vaccination with a single dose of JE-CV, with all (n=78) children seroprotected at the year 5 visit (geometric mean titers [GMT]: 2521/dil). There was no decrease of seroprotection rate over time (100% at 6months post-vaccination and 96.8% (90.3-98.9) at 5yearspost-vaccination). In JE-vaccine-naïve toddlers, a protective immune response persisted up to at least 5years in 58.8% (50.9-66.4) after a single-dose administration of JE-CV (GMT 26.71/dil; sensitivity analysis).

Conclusions: A single-dose of JE-CV as a booster following MBDV administration provided long-lasting immunity. In JE-vaccine-naïve toddlers, despite relatively high seroprotection rates persisting over time, a subsequent booster dose is recommended following a JE-CV primary vaccination for long-term protection. This study was registered on www.clinicaltrials.gov (NCT00621764).

Keywords: Attenuated; Children; Encephalitis virus, Japanese; Follow-up; Immunization; Vaccine.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Cross-Over Studies
  • Encephalitis Virus, Japanese / immunology
  • Encephalitis, Japanese / prevention & control*
  • Female
  • Follow-Up Studies
  • Formaldehyde
  • Humans
  • Immunization Schedule*
  • Immunization, Secondary
  • Infant
  • Japanese Encephalitis Vaccines / administration & dosage
  • Japanese Encephalitis Vaccines / adverse effects
  • Japanese Encephalitis Vaccines / genetics
  • Japanese Encephalitis Vaccines / immunology*
  • Male
  • Time Factors
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / adverse effects
  • Vaccines, Inactivated / immunology

Substances

  • Japanese Encephalitis Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated
  • Formaldehyde

Associated data

  • ClinicalTrials.gov/NCT00621764