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 PRNT50. 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.

Keywords: Japanese encephalitis vaccines; active immunization; attenuated vaccines; booster immunization; humoral immune response.

Figures

Figure 1. Disposition of children. JE-CV, Japanese encephalitis chimeric virus vaccine; FAS, full analysis set; D, day; AE, adverse event

Figure 2. Seroprotection and GMT levels after a booster dose of JE-CV. D, day; Y, year; GMT, geometric mean titer; PRNT50, plaque reduction neutralization test; error bars, 95% confidence intervals. One dose of JE-CV was given to eligible children who had previously received a single dose of JE-CV two years earlier. JE neutralizing antibody titers were assessed using a PRNT50. A neutralizing antibody titer of ≥ 10 1/dil is accepted as evidence of protection.‎ Results are for the PP (n = 340) for D0, D7, and D28 and for the FAS (n = 339) for Y1.

Figure 3. Immune response after vaccination with JE-CV in children who were seronegative at baseline. GMT, geometric mean titer and 95% CI; PRNT50, plaque reduction neutralization test; FAS for JE-CV primed children and PP for JE vaccine naïve children; error bars, 95% confidence intervals. One dose of JE-CV was given to children who previously received a single dose of JE-CV two years earlier, and to JE-vaccine naïve children. JE neutralizing antibody titers were assessed using a PRNT50. This figure shows the immune response in children who were seronegative at the start of the study.