DNA Vaccination against Theiler’s Murine Encephalomyelitis Virus Leads to Alterations in Demyelinating Disease

Abstract

ABSTRACT 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.