Growth characteristics of the chimeric Japanese encephalitis virus vaccine candidate, ChimeriVax-JE (YF/JE SA14--14--2), in Culex tritaeniorhynchus, Aedes albopictus, and Aedes aegypti mosquitoes.

Abstract

Abstract. The Japanese encephalitis (JE) virus vaccine candidate, ChimeriVax-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 replication in non-human primates, producing only a low-level viremia following peripheral inoculation. Although this reduces the likelihood that hematophagous 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 chimera is derived. In this study ChimeriVax-JE virus was compared to its parent 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. ChimeriVax-JE virus did not replicate following ingestion by any of the three mosquito species. Additionally, replication was not detected after IT inoculation of ChimeriVax-JE in the primary JE virus vector, Cx. tritaeniorhynchus. ChimeriVax-JE exhibited moderate growth following IT inoculation into Ae. aegypti and Ae. albopictus, reaching titers of 3.6-5.0 log 10 PFU/mosquito. There was no change in the virus genotype associated with replication in mosquitoes. Similar results were observed in mosquitoes of all three species that were IT inoculated or had orally ingested the YF 17D vaccine virus. In contrast, all mosquitoes either IT inoculated with or orally fed wild-type and vaccine JE viruses became infected, reaching maximum titers of 5.4-7.3 log 10 PFU/mosquito. These results indicate that ChimeriVax-JE virus is restricted in its ability to infect and replicate in these mosquito vectors. The low viremia caused by ChimeriVax-JE in primates and poor infectivity for mosquitoes are safeguards against secondary spread of the vaccine virus.

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

“…We further found that ChinDENV grew equally as well as the parent virus DENV-2 in various cell lines, with decreased peak replication titers compared with JEV. These results are consistent with the previous observations that chimeras exhibited growth characteristics similar to those of the viruses contributing structural protein genes (5,41), indicating that the reduction in plaque size and replication efficiency for ChinDENV compared to JEV are likely to be determined partly by the donor prM-E genes. In addition, the chimerization itself has been proved to contribute to the attenuation of chimeras (10,(42)(43)(44)(45)(46)(47)(48)(49)(50).…”

In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2

“…1b). These findings are consistent with the previous observations that chimeric flaviviruses could express the prM and E genes of heterologous flaviviruses, and exhibited growth-similar characteristics (Arroyo et al, 2001;Bhatt et al, 2000;Chambers et al, 1999;Guirakhoo et al, 2000;Pletnev et al, 2001Pletnev et al, , 2003.…”

Growth characteristics of ChimeriVax-DEN2 vaccine virus in Aedes aegypti and Aedes albopictus mosquitoes.

“…albopictus mosquitoes. 15 In these experiments, the replication kinetics of ChimeriVax™-DEN2 virus were shown to be similar to YF 17D and ChimeriVax™-JE viruses in Ae. albopictus C6/36 cells and in Ae.…”

“…Viral dissemination in the mosquito was determined by direct immunofluorescent antibody staining of head tissue as described previously. 15 Fluorescein isothiocyanate (FITC)-conjugated anti-YF virus mouse IgG ascitic fluid (Jackson Laboratories, West Grove, PA, lot 12185; diluted 1:15) was used to detect YF 17D virus. FITCconjugated antiflavivirus human sera (DFA; CDC, diluted 1:80) was used to detect DEN-2 and Chimerivax-DEN2 viruses.…”

“…15 ChimeriVax™-JE did not infect the JE vector mosquito Culex tritaeniorhynchus, and replication of ChimeriVax™-JE in the YF vectors Ae. aegypti and Ae.…”