Evaluation of Neurovirulence and Biodistribution of Venezuelan Equine Encephalitis Replicon Particles Expressing Herpes Simplex Virus Type 2 Glycoprotein D.
From: Vaccine Discovery Department, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA. kowalsj@wyeth.com
Vaccine
- Publish Date: Mar 2007
- ISSN: 0264-410X
- Volume: 25
- Issue: 12
- Pages: 2296-305
- Medium: Print
- Language: English
- Citation (JAMA): Kowalski Jacek, Adkins Karissa, Gangolli Seema, et al. Evaluation of Neurovirulence and Biodistribution of Venezuelan Equine Encephalitis Replicon Particles Expressing Herpes Simplex Virus Type 2 Glycoprotein D.. Vaccine Mar 2007;25:2296-305
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.
Mesh Headings (Keywords): Animals, Body Weight, Brain, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Injections, Intramuscular, Injections, Intravenous, Mice, RNA, Viral, Replicon, Reverse Transcriptase Polymerase Chain Reaction, Spinal Cord, Vaccines, Attenuated, Viral Envelope Proteins, Virus Replication
Check for Full Text / PubMed Unique Identifier (PMID): 17239997
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