Evaluation of neurovirulence and biodistribution of Venezuelan equine encephalitis replicon particles expressing herpes simplex virus type 2 glycoprotein D

• Published in: Vaccine 2007-03, Vol.25 (12), p.2296-2305
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Animals; Applied microbiology; Arboviral encephalitis; Arboviroses; Atoms & subatomic particles; Biological and medical sciences; Body Weight; Brain - metabolism; Brain - virology; Chromatography; Encephalitis Virus, Venezuelan Equine - genetics; Encephalitis Virus, Venezuelan Equine - immunology; Encephalomyelitis, Venezuelan Equine - immunology; Encephalomyelitis, Venezuelan Equine - prevention & control; Fundamental and applied biological sciences. Psychology; Gene expression; Genomes; Herpes simplex virus; Histopathology; Human viral diseases; Immunization; Infectious diseases; Injections, Intramuscular; Injections, Intravenous; Medical sciences; Mice; Microbiology; Miscellaneous; Neuropathology; Neurovirulence; Replicon - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Viral - genetics; RNA, Viral - metabolism; Spinal Cord - metabolism; Spinal Cord - virology; Tropical viral diseases; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Venezuelan equine encephalitis virus; Viral diseases; Viral Envelope Proteins - genetics; Viral replicon vector; Virology; Virus Replication - genetics
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2006.11.063

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.