Global Vaccine Safety

Safety profile of Japanese encephalitis (JE) chimeric vaccine

Extract from report of GACVS meeting of 11-12 December 2013, published in the WHO Weekly Epidemiological Record on 14 February 2014

During the June 2013 meeting of GACVS the safety profiles of 1 live attenuated and 2 inactivated Japanese encephalitis (JE) vaccines based on the SA 14-14-2 strain were considered, and the Committee concluded that there were no significant concerns regarding the safety profile of these vaccines.3 During the December 2013 meeting GACVS considered the safety profile of a novel chimeric JE vaccine (Imojev). This vaccine is a live vaccine construct using the yellow fever (YF) 17D and JE SA-14-14-2 vaccines strains. Construction of the vaccine involves insertion of the nucleic acid sequences encoding the envelope proteins (prM and E) of the JE SA 14-14-2 strain into the YF17D backbone, resulting in a chimeric vaccine virus which is attenuated and lacks neurotropic properties.

Pre-licensure and post-licensure safety and immunogenicity data for Imojev were presented. This vaccine is currently licensed in Australia, Malaysia, the Philippines and Thailand. Pre-licensure data are available for 2486 adults and 2248 children (9–18 months, at first dose). The vaccine is immunogenic and immunogenicity does not appear to be affected by concomitant administration of the measles/mumps/rubella (MMR) vaccine. Short-term safety data for injection site and systemic reactions (reported by >10% of vaccine recipients) were presented and showed that in the adult population, adverse reaction rates were significantly lower with Imojev than with a mouse brain-derived vaccine.4 There is limited post-licensure safety experience with Imojev, with approximately 49 000 doses administered to date, and a larger safety database will be necessary to evaluate the risk of rare adverse events.

GACVS expressed interest in receiving additional information about potential environmental safety issues relative to the use of a chimeric vaccine. These include the theoretical risk of reversion or genetic reassortment with wild-type JE viruses or other circulating flaviviruses that could result in the vaccine virus acquiring neurotropic and/or infectivity properties, and vaccine virus transmission through mosquito hosts. However the biological plausibility of this is remote, given the short duration of viraemia post vaccination and the limited potential for virus vaccine replication and dissemination within the mosquito.

Post-licensure studies are essential in countries were widespread use of a JE chimeric vaccine is planned or is currently implemented. In particular, post-licensure studies and surveillance should include active surveillance of cases of encephalitis along with a laboratory determination of the aetiology of the encephalitis. Safety data on JE vaccines (including but not limited to the chimeric vaccine) administered to immunocompromised persons and pregnant and lactating women are limited.

3 See No. 88, 2013, pp. 301-312.

4 Torresi J, McCarthy K, Feroldi E, et al. Immunogenicity, safety and tolerability in adults of a new single-dose, live-attenuated vaccine against Japanese encephalitis: randomised controlled phase 3 trials. Vaccine. 2010; 28:7993-8000.