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

The chimeric yellow fever (YF) 17D-dengue type 2 (ChimeriVax(TM)-DEN2) vaccine virus developed h Acambis. Inc. (Cambridge, MA) contains the prM and E genes of wild-type (wt) dengue 2 (DEN-2) (strain PUO-218) virus in the YF vaccine virus (strain 17D) backbone. The potential of ChimeriVax(TM)-DEN2 virus to infect and he transmitted by Aedes aegypti, the principal DEN and YF virus mosquito vector, and Aedes albopictus, a species that occurs in areas of active transmission of YF and DEN viruses, was evaluated. Mosquitoes were intrathoracically (IT) inoculated with virus or were fed a virus-laden blood meal, and the replication kinetics of ChimeriVax(TM)-DEN2 were compared with the wt DEN-2 and YF 17D vaccine viruses. Replication of YF 171) virus is attenuated in cultured Ae. albopictus C6/36 mosquito cells and in Ae. aegypti and Ae. albopictus mosquitoes, Growth of ChimeriVax(TM)-DEN2 virus similarly was restricted in C6/36 cells and in mosquitoes. ChimeriVax(TM)-DEN2 replicated in 50% of IT inoculated Ae. aegypti, and virus disseminated to head tissue in 36%, with a mean viral titer of 1.8 log(10) PFU/mosquito. Of mosquitoes. 16% of Ae. aegypti and 24% of Ae. albopictus were infected 14 days after a blood meal containing ChimeriVax(TM)-DEN2, but virus did not disseminate to head tissue. In contrast, DEN-2 replicated in all IT inoculated and orally infected Ae. aegypti (mean titer 5.5 log(10)) PFU/mosquito). and virus disseminated to head tissue in 95%. Of albopictus, 84%, were infected after a blood meal containing DEN-2 virus dissemination occurred in 36%. Replication of ChimeriVax(TM)DEN2 virus in mosquitoes corresponded to that of YF 17D vaccine virus. which is restricted in its ability to infect and replicate in mosquitoes. Therefore, transmission of ChimeriVaX(TM)-DEN2 virus by vector mosquitoes is unlikely.