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Journal of Virology, February 1999, p. 993-1000, Vol. 73, No. 2
Department of Neurology, University of Utah
School of Medicine, Salt Lake City, Utah 84132
Received 18 August 1998/Accepted 23 October 1998
Although the etiology of multiple sclerosis (MS) is not known,
several factors play a role in this disease: genetic contributions, immunologic elements, and environmental factors. Viruses and virus infections have been associated with the initiation and/or enhancement of exacerbations in MS. Theiler's murine encephalomyelitis virus (TMEV) infection of mice is one of the animal models used to mimic MS.
In other animal model systems, DNA vaccination has been used to protect
animals against a variety of virus infections. To explore the utility
of DNA vaccination, we have constructed eukaryotic expression vectors
encoding the TMEV capsid proteins VP1, VP2, and VP3. SJL/J mice were
vaccinated intramuscularly once, twice, or three times with the
different capsid protein cDNAs. This was followed by intracerebral TMEV
infection to determine the effects of DNA vaccination on the course of
TMEV-induced central nervous system (CNS) demyelinating disease. We
found that vaccination of mice three times with cDNA encoding VP2 led
to partial protection of mice from CNS demyelinating disease as
determined by a decrease in clinical symptoms and histopathology.
Vaccination of mice with cDNA encoding VP3 also led to a decrease in
clinical symptoms. In contrast, mice vaccinated with cDNA encoding VP1
experienced a more severe disease with an earlier onset of clinical
signs and enhanced histopathology compared with control mice. There was
no correlation between anti-TMEV antibody titers and disease course.
These results indicate that DNA immunization can modify chronic
virus-induced demyelinating disease and may eventually lead to
potential treatments for illnesses such as MS.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
DNA Vaccination against Theiler's Murine
Encephalomyelitis Virus Leads to Alterations in Demyelinating
Disease
*
Corresponding author. Mailing address: Department of
Neurology, 3R330 School of Medicine, University of Utah, 30 N. 1900 E., Salt Lake City, UT 84132. Phone: (801) 585-3305. Fax: (801) 585-3311. E-mail: Robert.Fujinami{at}hsc.utah.edu.
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