Memory immune response and safety of a booster dose of Japanese encephalitis chimeric virus vaccine (JE-CV) in JE-CV-primed children

Marcy l'Etoile, France.
Human Vaccines & Immunotherapeutics (Impact Factor: 2.37). 02/2013; 9(4). DOI: 10.4161/hv.23087
Source: PubMed


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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    • "Against JE, while a slightly lower seroprotection rate was seen at M12 after co-administration than in the other two groups, the GMTs remain well above the threshold for protection. It is also comparable with data from previous studies assessing a single dose of JE-CV for primary immunization in Asian toddler populations living in endemic areas [6] [14]. A booster vaccination is recommended after 12 months, and another when children are 6 years old. "
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    ABSTRACT: Japanese encephalitis (JE) is the most important cause of viral encephalitis in Asia. In this randomized, open-label, multicenter trial in 550 children aged 12 to 18 months in Taiwan, children received one dose of JE-CV and one dose of MMR vaccine. Vaccines were either administered separately 6 weeks apart (Groups 'JE-CV' and 'MMR', named after which vaccine was given first), or concomitantly (Group 'Co-Ad'). JE neutralizing antibody titers were assessed using PRNT50. MMR antibody levels determined by ELISA. All groups had low seroprotection/seropositivity rates (<10%) before vaccination for all antigens. Forty two days after vaccination, on either Study Day 42 or 84, seroconversion rates for all antigens were high in all groups, irrespective of the order of vaccinations. Seroconversion for JE ranged from 96.9% in Group Co-Ad on D42 to 100% in Group MMR. Non-inferiority was demonstrated for all analyses as the lower bound of the 95% CI of the difference in seroconversion rates between groups was above the pre-defined limit of -10.0%. The immune responses remained high for all antigens and well above the level of protection 12 months after vaccination in all groups. There were no safety concerns. JE-CV is safe and induces a strong protective immune response which persists over 1 year when co-administered with MMR vaccine. registration: NCT01188343.
    Vaccine 03/2014; 32(41). DOI:10.1016/j.vaccine.2014.02.085 · 3.62 Impact Factor
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    • "In a subsequent Phase III study in Thailand and the Philippines involving 1,200 JE vaccine naïve children aged 12–18 months, the seroconversion rate to a single dose of ChimeriVax™-JE was 95% (95% CI 93–96) with a GMT value of 214 (95% CI 168–271) [38] against the homologous vaccine strain. In a follow-up study, the effect of booster vaccination with ChimeriVax™-JE in children aged 36–42 months who had received the primary vaccination 2 years prior was reported [52]. Of the 350 children studied, 80% of primary vaccinees had seroprotective antibodies at study commencement, albeit with low GMT values, 39 (95% CI 34–46). "
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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: Evaluation of: Larena M, Prow NA, Hall RA, Petrovsky N, Lobigs M. JE-ADVAX Vaccine protection against Japanese encephalitis virus mediated by memory B cells in the absence of CD8(+) T cells and pre-exposure neutralizing antibody. J. Virol. 87(8), 4395-4402 (2013). Japanese encephalitis (JE) virus requires dissemination within the host via the circulation for disease development. Thus, a serum-neutralizing antibody is an effective factor to protect against disease. Current licensed JE vaccines induce neutralizing antibodies and titers of 1:10 or higher are the recommended immunological correlate of protection. In this paper, the authors demonstrated, using a highly susceptible knockout mouse model, that memory B cells are required for disease protection and that detectable neutralizing antibodies at the time of challenge are dispensable. The authors proposes that the extent of memory B cells would be an alternative and better immunological correlate for evaluating the efficacy of JE vaccine candidates in clinical trials.
    Expert Review of Vaccines 08/2013; 12(8). DOI:10.1586/14760584.2013.814828 · 4.21 Impact Factor
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