Memory immune response and safety of a booster dose of Japanese encephalitis chimeric virus vaccine (JE-CV) in JE-CV-primed children
ABSTRACT Japanese encephalitis chimeric virus vaccine (JE-CV) is a licensed vaccine indicated in a single dose administration for primary immunization. This controlled phase III comparative trial enrolled children aged 36-42 mo in the Philippines. 345 children who had received one dose of JE-CV in a study two years earlier, received a JE-CV booster dose. 105 JE-vaccine-naïve children in general good health were randomized to receive JE-CV (JE-vaccine naïve group; 46 children) or varicella vaccine (safety control group; 59 children). JE neutralizing antibody titers were assessed using PRNT 50. Immunological memory was observed in children who had received the primary dose of JE-CV before. Seven days after the JE-CV booster dose administration, 96.2% and 66.8% of children were seroprotected and had seroconverted, respectively, and the geometric mean titer (GMT) was 231 1/dil. Twenty-eight days after the JE-CV booster dose seroprotection and seroconversion were achieved in 100% and 95.3% of children, respectively, and the GMT was 2,242 1/dil. In contrast, only 15.4% of JE-CV-vaccine naïve children who had not received any prior JE vaccine were seroprotected seven days after they received JE-CV. One year after receiving the JE-CV booster dose, 99.4% of children remained seroprotected. We conclude that JE-CV is effective and safe, both as a single dose and when administrated as a booster dose. A booster dose increases the peak GMT above the peak level reached after primary immunization and the antibody persistence is maintained at least one year after the JE-CV booster dose administration. Five year follow up is ongoing.
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ABSTRACT: The Japanese encephalitis virus (JEV) is endemic in many countries in southern Asia and the western Pacific Rim, with new spread to previously unrecognized countries. It is an important cause of childhood neurological disease associated with permanent neurological sequelae and death. Fortunately, JE is a vaccine-preventable disease. The ChimeriVax™-JE (Sanofi Pasteur, Lyon, France) is a live-attenuated chimeric vaccine derived from the live-attenuated yellow fever virus, YF17D, which expresses the envelope proteins of the attenuated JEV vaccine strain, SA14-14-2. It is a safe, well-tolerated vaccine that is highly immunogenic in adults and children. The average geometric mean neutralizing antibody titer (GMT) in adults is 1,392 and over 90% of adults remain seroprotected 5 years after vaccination. In children and toddlers, more than 80% remain seroprotected 2 years after primary vaccination and demonstrate a robust and durable anamnestic response (>500-fold rise in GMT) with 99.1% seroprotection rates 1 year after a booster vaccine dose. The ChimeriVax™-JE is effective in children living in endemic regions where the vaccine could possibly be integrated into existing childhood vaccination programs. ChimeriVax™-JE is also indicated for travelers at risk of JE infection.12/2013; 2(2):145-58. DOI:10.1007/s40121-013-0018-2
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ABSTRACT: Japanese encephalitis (JE) is one of the most important viral encephalitides in Asia. Two live-attenuated vaccines have been developed and licensed for use in countries in the region. Given the advancement of immunization of humans with increasing use of live-attenuated vaccines to prevent JE, there is increased interest to define quality standards for their manufacture, testing, nonclinical studies, and clinical studies to assess their efficacy and safety in humans. To this end, WHO convened a meeting with a group of international experts in February 2012 to develop guidelines for evaluating the quality, safety and efficacy of live-attenuated JE virus vaccines for prevention of human disease. This report summarizes collective views of the participants on scientific and technical issues that need to be considered in the guidelines.Biologicals 11/2013; 41(6):450–457. DOI:10.1016/j.biologicals.2013.06.001 · 1.41 Impact Factor
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ABSTRACT: 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. In this phase III, observer-blinded trial, 300 children at the age of 9-18 months were randomized 1:1 to receive one dose of JE-CV or SA14-14-2. JE neutralizing antibody titers were assessed using PRNT50. The primary endpoint was the non-inferiority of seroconversion against JE on D28 after JE-CV compared to SA14-14-2, as assessed using the 95% confidence interval of the difference between the groups. Safety and reactogencity were described in each group using conventional methods, including the reporting of solicited and unsolicited adverse events. The seroconversion rate on D28 was 99.2% in each group. Non-inferiority was demonstrated as the difference between the JE-CV and SA14-4-2 groups was -0.012 percentage points (95%CI: -3.6; 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 D28 after vaccination were 507 (1/dil) in the JE-CV group and 370 (1/dil) in the SA14-14-2 group, decreasing by respectively 4.3-fold and 3.6-fold 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 to SA14-14-2. A single dose of JE-CV elicited a non-inferior immune response compared to SA14-14-2, and had a satisfactory safety profile.The Pediatric Infectious Disease Journal 04/2014; 33(6). DOI:10.1097/INF.0000000000000276 · 3.14 Impact Factor