Kowalski Jacek, Adkins Karissa, Gangolli Seema, Ren Jian, Arendt Heather, DeStefano Joanne, Obregon Jennifer, Tummolo Donna, Natuk Robert J, Brown Tom P, Parks Christopher L, Udem Stephen A, Long Deborah
Vaccine Discovery Department, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA.
Vaccine. 2007 Mar 8;25(12):2296-305. doi: 10.1016/j.vaccine.2006.11.063. Epub 2006 Dec 12.
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.
