Safety and immunogenicity of a single administration of live-attenuated Japanese encephalitis vaccine in previously primed 2- to 5-year-olds and naive 12- to 24-month-olds: multicenter randomized controlled trial.
BACKGROUND
Safe and effective Japanese encephalitis (JE) vaccines are needed to protect populations living in or visiting endemic areas. A live-attenuated JE-chimeric virus vaccine (JE-CV) has been developed with a single-dose regimen.


METHODS
In an open-label, crossover study, 100 children aged 2 to 5 years with a history of 2-dose primary vaccination with mouse-brain derived inactivated JE vaccine according to the Thai Expanded Program for Immunization schedule, and 200 JE vaccination-naive 12- to 24-month-old toddlers were randomized 1:1 to receive JE-CV, containing ≥4 log10 plaque forming units, 1 month before or after hepatitis A control vaccine. Neutralizing antibody titers were assessed using PRNT50 (titers expressed in inverse of dilution) before and 28 days after JE-CV, and at months 7 and 12.


RESULTS
All 2- to 5-year-olds and 96% of 12- to 24-month-olds were seroprotected (titer ≥10) 28 days after JE-CV administration, and geometric mean titers (GMT) (95% confidence interval) in these age groups were 2634 (1928-3600) and 281 (219-362), respectively. One year later, seroprotection rates in the 2 age groups were 97% and 84% and GMTs were 454 and 62.3, respectively. Vaccine-induced antibodies neutralized a panel of wild-type JE isolates. There were no vaccine-related serious adverse events. Reactogenicity of JE-CV was comparable with that of the inactivated hepatitis A vaccine.


CONCLUSIONS
A single administration of JE-CV has a good safety profile and elicits a protective immune response in both JE-naive toddlers and JE-primed young children.
Chokephaibulkit
Kulkanya
K
Division of Infectious Diseases, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Sirivichayakul
Chukiat
C
Thisyakorn
Usa
U
Sabchareon
Arunee
A
Pancharoen
Chitsanu
C
Bouckenooghe
Alain
A
Gailhardou
Sophia
S
Boaz
Mark
M
Feroldi
Emmanuel
E
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D002675:Child, Preschool; D018592:Cross-Over Studies; D004672:Encephalitis, Japanese / Q000276:immunology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D013785:Thailand; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated