Evaluation of neurovirulence and biodistribution of Venezuelan equine encephalitis replicon particles expressing herpes simplex virus type 2 glycoprotein D.
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.
Kowalski
Jacek
J
Vaccine Discovery Department, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. kowalsj@wyeth.com
Adkins
Karissa
K
Gangolli
Seema
S
Ren
Jian
J
Arendt
Heather
H
DeStefano
Joanne
J
Obregon
Jennifer
J
Tummolo
Donna
D
Natuk
Robert J
RJ
Brown
Tom P
TP
Parks
Christopher L
CL
Udem
Stephen A
SA
Long
Deborah
D
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
D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2