title: Substitution of wild-type yellow fever Asibi sequences for 17D vaccine sequences in ChimeriVax-dengue 4 does not enhance infection of Aedes aegypti mosquitoes.
abstract: To address concerns that a flavivirus vaccine/wild-type recombinant virus might have a high mosquito infectivity phenotype, the yellow fever virus (YFV) 17D backbone of the ChimeriVax-dengue 4 virus was replaced with the corresponding gene sequences of the virulent YFV Asibi strain. Field-collected and laboratory-colonized Aedes aegypti mosquitoes were fed on blood containing each of the viruses under investigation and held for 14 days after infection. Infection and dissemination rates were based on antigen detection in titrated body or head triturates. Our data indicate that, even in the highly unlikely event of recombination or substantial backbone reversion, virulent sequences do not enhance the transmissibility of ChimeriVax viruses. In light of the low-level viremias that have been observed after vaccination in human volunteers coupled with low mosquito infectivity, it is predicted that the risk of mosquito infection and transmission of ChimeriVax vaccine recombinant/revertant viruses in nature is minimal.
authors.affiliation: Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McGee
authors.forename: Konstantin
authors.initials: K
authors.lastname: Tsetsarkin
authors.forename: Dana L
authors.initials: DL
authors.lastname: Vanlandingham
authors.forename: Kate L
authors.initials: KL
authors.lastname: McElroy
authors.forename: Jean
authors.initials: J
authors.lastname: Lang
authors.forename: Bruno
authors.initials: B
authors.lastname: Guy
authors.forename: Thierry
authors.initials: T
authors.lastname: Decelle
authors.forename: Stephen
authors.initials: S
authors.lastname: Higgs
mesh_terms: D000330:Aedes / Q000821:virology*; D000818:Animals; D002678:Chimera / Q000235:genetics / Q000821:virology; D003715:Dengue / Q000635:transmission / Q000662:veterinary; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology*; D007303:Insect Vectors / Q000821:virology*; D014613:Vaccines, Attenuated / Q000235:genetics*; D014766:Viremia; D053060:West Nile Virus Vaccines / Q000235:genetics*; D015004:Yellow Fever / Q000276:immunology / Q000662:veterinary; D022341:Yellow Fever Vaccine / Q000235:genetics*; D015005:Yellow fever virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity
chemical_list: C445780:ChimeriVax; C528874:ChimeriVax-DEN4 vaccine; D014613:Vaccines, Attenuated; D053060:West Nile Virus Vaccines; D022341:Yellow Fever Vaccine