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



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 log10plaque forming units, 1month before or after hepatitis A control vaccine.



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).



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).
Division of Infectious Diseases, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Electronic address: kulkanya.cho@mahidol.ac.th.
Kulkanya
K
Chokephaibulkit
Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand. Electronic address: chukiat.sir@mahidol.ac.t.
Chukiat
C
Sirivichayakul
Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand. Electronic address: uthisyakorn@gmail.com.
Usa
U
Thisyakorn
Department of Pediatrics, Chulalongkorn Hospital, Bangkok, Thailand. Electronic address: Chitsanu.P@chula.ac.th.
Chitsanu
C
Pancharoen
Global Clinical Immunology, Sanofi Pasteur, Swiftwater, PA, USA. Electronic address: markjboaz@gmail.com.
Mark
M
Boaz
Medical Affairs & Clinical Sciences, Sanofi Pasteur, Singapore. Electronic address: Alain.Bouckenooghe@sanofipasteur.com.
Alain
A
Bouckenooghe
Clinical Sciences, Sanofi Pasteur, Marcy l'Etoile, France. Electronic address: Emmanuel.Feroldi@sanofipasteur.com.
Emmanuel
E
Feroldi
D002675:Child, Preschool; D018592:Cross-Over Studies; D004664:Encephalitis Virus, Japanese / Q000276:immunology; D004672:Encephalitis, Japanese / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D005557:Formaldehyde; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007223:Infant; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D008297:Male; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D022321:Japanese Encephalitis Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated; D005557:Formaldehyde
Attenuated; Children; Encephalitis virus, Japanese; Follow-up; Immunization; Vaccine