The Pediatric Infectious Disease Journal •  Volume 33, Number 6, June 2014 www.pidj.com | 643 VACCINE REPORTS 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 com- pared 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 PRNT 50 . 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 inter- val: -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 vaccina- tion 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 com- pared 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. Key Words: Japanese encephalitis vaccine, phase 3 trial, children, immu- nogenicity, safety (Pediatr Infect Dis J 2014;33:643–649) J apanese encephalitis virus (JEV) is the most important cause of viral encephalitis in Asia and is a significant cause of childhood morbidity and mortality. 1,2 Inactivated, mouse brain-derived JE vac- cine (MBDV) was found to be highly effective and was included in the expanded program of immunization (EPI) for children in several countries including Thailand; 3,4 MBDV is given with a 2-dose regimen at 12–18 months of age in Thailand, followed by a booster 1 year later. Due to safety concerns and the need for multiple injections, newer vaccines are desirable to replace MBDV. The SA14-14-2 live-attenuated JE vaccine (Chengdu Institute of Biological Products, People’s Republic of China) is licensed in Thailand and other Asian countries. In Thailand, the immunization schedule of SA14-14-2 vaccine is a 2-dose regimen, the second dose (booster dose) being given between 3 months and 1 year after the primary immunization. JE-CV, a live-attenuated JE chimeric virus vaccine, has been developed to give protection against JE with an improved overall safety profile. This vaccine virus was developed by replac- ing the premembrane (prM) and envelope (E) coding sequences from the yellow fever vaccine virus (strain 17D) genome with the corresponding sequences from the SA14-14-2 JEV strain. 5–7 JE-CV is grown in Vero cells in serum-free conditions. 5–7 In adults, a single dose of JE-CV induced 99.1% seroconversion 30 days after subcutaneous administration, and >93% of adults had seroconverted 14 days after vaccination. 8 Seroconversion after a single dose of JE-CV was noninferior to seroconversion after 3 doses of a licensed MBDV JE vaccine (JE-VAX) considered as a standard of care of JE vaccines at the time of the study as this was the main vaccine that was routinely used in the EPI programs of various endemic countries. 8 JE-CV had lower reactogenicity at the injection site than the inactivated MBDV, and systemic reac- togenicity of JE-CV was similar to that of a placebo. 8 Data from the first studies conducted in pediatric populations in JE endemic countries showed 95% seroconversion in JE vaccine naïve tod- dlers at the age of 12 months and 100% seroprotection in 2- to 5-year-old children previously vaccinated with MBDV and in whom the seroprotection rate before the JE-CV injection was 85.6%; no safety concerns were identified during these studies. 9,10 Immunological memory and a robust anamnestic response were observed in children 2 years after a single dose of JE-CV for pri- mary immunization at 12–18 months of age. 11 In 2010, JE-CV was approved by the Therapeutic Goods Administration (TGA) Copyright © 2014 by Lippincott Williams & Wilkins ISSN: 0891-3668/14/3306-0643 DOI: 10.1097/INF.0000000000000276 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 Emmanuel Feroldi, MD,* Chitsanu Pancharoen, MD,† Pope Kosalaraksa, MD,‡ Kulkanya Chokephaibulkit, MD,§ Mark Boaz, PhD,¶ Claude Meric, MD,‖ Yanee Hutagalung, MD,** and Alain Bouckenooghe, MD** Accepted for publication January 8, 2014. From the *Sanofi Pasteur Clinical Development Department, Marcy l’Etoile, France; †Chulalongkorn Hospital, Bangkok; ‡Srinagarind Hospital, Khon Kaen University, Khon Kaen; §Siriraj Hospital, Bangkok, Thailand; ¶Sanofi Pasteur Global Clinical Immunology Department, Swiftwater, PA; ‖Sanofi Pasteur Europe New Vaccines Projects, Marcy L’Etoile, France; and **Sanofi Pasteur Clinical Development Department, Singapore. The study sponsor and manufacturer of the investigational vaccine, Sanofi Pas- teur, was involved in the trial design, the management and analysis of data and in the decision to publish. This article was prepared with the assistance of a professional medical writer, funded by Sanofi Pasteur. E.F., M.B., C.M., Y.H. and A.B. are employees of Sanofi Pasteur. P.K. has previ- ously received payment from Sanofi Pasteur for 1 lecture and funding for attending 1 international meeting. The authors have have no other funding or conflicts of interest to declare. Trial registration number was ClinicalTrials.gov: NCT01092507. Address for correspondence: Emmanuel Feroldi, MD, Clinical Development Department, Sanofi Pasteur 1541 Avenue Marcel Merieux 69280 Marcy L’Etoile, France. E-mail: emmanuel.feroldi@sanofipasteur.com.