title: Evaluation of neurovirulence and biodistribution of Venezuelan equine encephalitis replicon particles expressing herpes simplex virus type 2 glycoprotein D.
abstract: The safety of a propagation-defective Venezuelan equine encephalitis virus (VEEV) replicon particle vaccine was examined in mice. After intracranial inoculation we observed approximately 5% body weight loss, modest inflammatory changes in the brain, genome replication, and foreign gene expression. These changes were transient and significantly less severe than those caused by TC-83, a live-attenuated vaccinal strain of VEEV that has been safely used to immunize military personnel and laboratory workers. Replicon particles injected intramuscularly or intravenously were detected at limited sites 3 days post-administration, and were undetectable by day 22. There was no evidence of dissemination to spinal cord or brain after systemic administration. These results demonstrate that propagation-defective VEEV replicon particles are minimally neurovirulent and lack neuroinvasive potential.
authors.affiliation: Vaccine Discovery Department, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. kowalsj@wyeth.com
authors.forename: Jacek
authors.initials: J
authors.lastname: Kowalski
authors.forename: Karissa
authors.initials: K
authors.lastname: Adkins
authors.forename: Seema
authors.initials: S
authors.lastname: Gangolli
authors.forename: Jian
authors.initials: J
authors.lastname: Ren
authors.forename: Heather
authors.initials: H
authors.lastname: Arendt
authors.forename: Joanne
authors.initials: J
authors.lastname: DeStefano
authors.forename: Jennifer
authors.initials: J
authors.lastname: Obregon
authors.forename: Donna
authors.initials: D
authors.lastname: Tummolo
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Natuk
authors.forename: Tom P
authors.initials: TP
authors.lastname: Brown
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Parks
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Udem
authors.forename: Deborah
authors.initials: D
authors.lastname: Long
mesh_terms: D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism / Q000821:virology; D004666:Encephalitis Virus, Venezuelan Equine / Q000235:genetics / Q000276:immunology*; D004685:Encephalomyelitis, Venezuelan Equine / Q000276:immunology* / Q000517:prevention & control; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D051379:Mice; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012093:Replicon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism / Q000821:virology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2