Jacek Kowalski,
Karissa Adkins,
Seema Gangolli, Jian Ren,
Heather Arendt,
Joanne DeStefano,
Jennifer Obregon,
Donna Tummolo,
Robert J Natuk,
Tom P Brown,
Christopher L Parks,
Stephen A Udem,
Deborah Long
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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.
Vaccine 04/2007; 25(12):2296-305. · 3.77 Impact Factor
