Growth characteristics of the chimeric Japanese encephalitis virus vaccinecandidate, ChimeriVax (TM)-JE (YF/JE SAL4-14-2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes

The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax(TM)-JE, which consists of a yellow fever (YF) 17D virus backbone containing the prM and E genes from the JE vaccine strain JE SA14-14-2, exhibits restricted r eplication in non-human primates, producing only a low-level viremia follow ing peripheral inoculation. Although this reduces the likelihood that hemat ophagous insects could become infected by feeding on a vaccinated host, it is prudent to investigate the replication kinetics of the vaccine virus in mosquito species that are known to vector the viruses from which the chimer a is derived. In this study ChimeriVax(TM)-JE virus was compared to its par ent viruses, as well as to wild-type JE virus, for its ability to replicate in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes . Individual mosquitoes were exposed to the viruses by oral ingestion of a virus-laden blood meal or by intrathoracic (IT) virus inoculation. ChimeriV ax(TM)-JE virus did not replicate following ingestion by any of the three m osquito species. Additionally, replication was not detected after IT inocul ation of ChimeriVax(TM)-JE in the primary JE virus vector, Cx. tritaeniorhy nchus. ChimeriVax(TM)-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log(10) PF U/mosquito. There was no change in the virus genotype associated with repli cation in mosquitoes. Similar results were observed in mosquitoes of all th ree species that were IT inoculated or had orally ingested the YF 17D vacci ne virus. In contrast, all mosquitoes either IT inoculated with or orally f ed wild-type and vaccine JE viruses became infected, reaching maximum titer s of 5.4-7.3 log(10) PFU/mosquito. These results indicate that ChimeriVax(T M)-JE virus is restricted in its ability to infect and replicate in these m osquito vectors. The low viremia caused by ChimeriVax(TM)-JE in primates an d poor infectivity for mosquitoes are safeguards against secondary spread o f the vaccine virus.