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.
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.
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.
Emmanuel
E
Feroldi
Chitsanu
C
Pancharoen
Pope
P
Kosalaraksa
Kulkanya
K
Chokephaibulkit
Mark
M
Boaz
Claude
C
Meric
Yanee
Y
Hutagalung
Alain
A
Bouckenooghe
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D002675:Child, Preschool; D004672:Encephalitis, Japanese / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D007223:Infant; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008297:Male; D013785:Thailand / Q000453:epidemiology
D000914:Antibodies, Viral; D022321:Japanese Encephalitis Vaccines