Long term immunity following a booster dose of the inactivated Japanese Encephalitis vaccine IXIARO®, IC51.

INTRODUCTION: IXIARO (IC51), a recently approved inactivated Japanese Encephalitis vaccine, is immunogenic and safe in a 0/28 days primary immunization schedule. Neutralizing antibody titers decline with time and booster doses are likely needed to enhance persistence of immunity. OBJECTIVES: To assess the effect of a booster dose on neutralizing JE antibody titers for up to 12 months after boostering. METHODS: In this phase III trial, 198 subjects, who had received primary immunization in a preceding randomized trial, were boosted with IXIARO 15 months after the primary immunization. Neutralizing antibody titers were assessed by plaque-reduction neutralisation test, PRNT. RESULTS: Prior to the booster dose, 69.2% (137/198) of subjects had PRNT50 titers ≥ 1:10. One month after the booster, the rate of subjects with PRNT50 ≥ 1:10 (recognized as a protective titer) was 100%. This rate remained high at 98.5% at 6 and 12 months; GMTs were 22.5 before the booster and 900, 487 and 361 at 1, 6 and 12 months after the booster, respectively. CONCLUSION: A booster dose of IXIARO at 15 months after primary immunization was highly immunogenic with GMTs >5-fold higher than those seen immediately after primary immunization, and remained at high levels for at least 12 months after the booster.

Safety analysis of a Vero-cell culture derived Japanese encephalitis vaccine, IXIARO (IC51), in 6 months of follow-up.

Japanese encephalitis (JE) is the most common viral encephalitis in Asia. IXIARO is a Vero cell-derived, inactivated JE virus vaccine which has recently been approved in the US, Europe, Canada and Australia (trade name JESPECT). This overview of the safety and tolerability of IXIARO, for 6 months after the first vaccination in 7 Phase III trials, includes: 3558 subjects with at least one IXIARO vaccination, 435 subjects with a JE-VAX (manufactured by BIKEN, distributed by Sanofi Pasteur) vaccination, and 657 with phosphate-buffered saline solution with 0.1% Al(OH)(3) (PBS+Alum) control vaccination. The percentage of subjects reporting solicited local adverse events (AEs) with IXIARO (54%) was similar to PBS+Alum vaccination (56%) as were solicited systemic adverse events (40% IXIARO; 40% PBS+Alum vaccination). JE-VAX showed a higher frequency of subjects with solicited local adverse events (61%) but a slightly lower frequency of subjects with solicited systemic adverse events (36%). The frequency of subjects with any solicited and unsolicited AE with IXIARO (64%) was also similar to PBS+Alum vaccination (61%) and JE-VAX (64%); as for subjects with serious AEs (1% IXIARO; 2% PBS+Alum vaccination, 1% JE-VAX). No serious allergic reactions were observed in any group. This safety analysis indicates that IXIARO has a favorable safety profile, comparable to PBS+Alum control vaccination and appears to have a better local tolerability profile than JE-VAX.

Long-term immunity and immune response to a booster dose following vaccination with the inactivated Japanese encephalitis vaccine IXIARO, IC51.

IC51 (IXIARO, JESPECT) is a recently approved prophylactic Japanese encephalitis virus vaccine with a two-vaccine primary immunization regimen. In this phase 3 trial, after primary immunization with a Day 0/28 dose schedule, seroprotection rates were 83%, 58% and 48% at Month 6, Month 12 and Month 24, respectively. A booster dose at Month 11 and/or Month 23 in subjects with neutralizing antibody titers below the limit of detection (defined as a serum dilution giving a 50% reduction of plaque counts in a plaque reduction neutralization test [PRNT50]<1:10) led to 100% seroconversion. After a single-dose immunization (incomplete primary immunization), only 9% of subjects were seroprotected at Month 6; however, a booster dose at Month 11 led to seroconversion in 99% of subjects. Hence, subjects with incomplete primary immunization can complete their schedule within at least 11 months.