Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial.

ABSTRACT

BACKGROUND: Japanese encephalitis virus (JEV) is the leading cause of viral encephalitis in southeast Asia. Although no treatment is currently available, vaccination effectively prevents the disease. In a non-inferiority study, we aimed to compare the safety and immunogenicity of a novel, second-generation, inactivated candidate vaccine for JEV with a licensed, mouse-brain-derived vaccine. METHODS: We included 867 adults in a multicentre, multinational, observer-blinded, randomised controlled phase III trial. Study sites were located in the USA, Germany, and Austria. Volunteers received either the JEV test vaccine intramuscularly on a two-dose schedule (on days 0 and 28; n=430) or the licensed vaccine subcutaneously according to its recommended three-dose schedule (on days 0, 7, and 28; n=437). The primary endpoint was immunogenicity, with respect to neutralising JEV-specific antibodies assessed by a plaque-reduction neutralisation test, which was assessable in 725 patients in the per-protocol population. This trial is registered as a clinical trial, EudraCT number 2004-002474-36. FINDINGS: The safety profile of the test vaccine was good, and its local tolerability profile was more favourable than that of the licensed vaccine. Frequency of adverse events was similar between treatment groups, and vaccine-related adverse events were generally mild. The seroconversion rate of the test vaccine was 98% compared with 95% for the licensed vaccine on day 56 (95% CI for the difference -1.33 to 3.43). Geometric mean titre for recipients of the test vaccine was 244 (range 5-19 783), compared with 102 (5-1864) for the licensed vaccine (ratio 2.3 [95% CI 1.967-2.75]). INTERPRETATION: The test JEV vaccine has a promising immunogenicity and safety profile.