title: Growth characteristics of ChimeriVax-DEN2 vaccine virus in Aedes aegypti and Aedes albopictus mosquitoes.
abstract: The chimeric yellow fever (YF) 17D-dengue type 2 (ChimeriVax-DEN2) vaccine virus developed by 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-DEN2 virus to infect and be 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-DEN2 were compared with the wt DEN-2 and YF 17D vaccine viruses. Replication of YF 17D virus is attenuated in cultured Ae. albopictus C6/36 mosquito cells and in Ae. aegypti and Ae. albopictus mosquitoes. Growth of ChimeriVax-DEN2 virus similarly was restricted in C6/36 cells and in mosquitoes. ChimeriVax-DEN2 replicated in 56% of IT inoculated Ae. aegypti, and virus disseminated to head tissue in 36%, with a mean viral titer of 1.8 log10 PFU/mosquito. Of mosquitoes, 16% of Ae. aegypti and 24% of Ae. albopictus were infected 14 days after a blood meal containing ChimeriVax-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 log10 PFU/mosquito), and virus disseminated to head tissue in 95%. Of Ae. albopictus, 84% were infected after a blood meal containing DEN-2 virus; dissemination occurred in 36%. Replication of ChimeriVax-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-DEN2 virus by vector mosquitoes is unlikely.
authors.affiliation: Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado 80522, USA.
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Johnson
authors.forename: Trudy V
authors.initials: TV
authors.lastname: Chambers
authors.forename: Mary B
authors.initials: MB
authors.lastname: Crabtree
authors.forename: Tejal R
authors.initials: TR
authors.lastname: Bhatt
authors.forename: Farshad
authors.initials: F
authors.lastname: Guirakhoo
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Barry R
authors.initials: BR
authors.lastname: Miller
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D017931:DNA Primers; D003715:Dengue / Q000517:prevention & control*; D003716:Dengue Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D005814:Genes, Viral; D007150:Immunohistochemistry; D017422:Sequence Analysis, DNA; D013045:Species Specificity; D014765:Viral Vaccines; D014779:Virus Replication
chemical_list: D017931:DNA Primers; D014765:Viral Vaccines