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DNA vaccination against Theiler's murine encephalomyelitis virus leads to alterations in demyelinating disease
N D Tolley1, I Tsunoda, R S Fujinami
1Department of Neurology, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA.
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.
Insights
DNA vaccination targeting specific viral proteins offers a potential therapeutic strategy for demyelinating diseases like multiple sclerosis (MS). Vaccination with VP2 or VP3 proteins showed protective effects, while VP1 exacerbated disease in a mouse model.
Area of Science:
- Neuroimmunology
- Virology
- Vaccine Development
Background:
- Multiple sclerosis (MS) etiology is multifactorial, involving genetic, immunologic, and environmental factors.
- Viral infections are implicated in MS initiation and exacerbation.
- Theiler's murine encephalomyelitis virus (TMEV) infection in mice serves as a model for MS.
Purpose of the Study:
- To investigate the efficacy of DNA vaccination using TMEV capsid proteins (VP1, VP2, VP3) in a mouse model of MS.
- To determine if DNA immunization can alter the course of TMEV-induced central nervous system (CNS) demyelinating disease.
Main Methods:
- Construction of eukaryotic expression vectors encoding TMEV capsid proteins VP1, VP2, and VP3.
- Intramuscular vaccination of SJL/J mice with capsid protein cDNAs (once, twice, or thrice).
- Intracerebral TMEV infection followed by assessment of clinical symptoms and histopathology.
Main Results:
- Three-time vaccination with VP2 cDNA conferred partial protection, reducing clinical symptoms and CNS demyelination.
- VP3 cDNA vaccination also decreased clinical symptoms.
- VP1 cDNA vaccination resulted in more severe disease, earlier onset, and enhanced pathology compared to controls.
- Anti-TMEV antibody titers did not correlate with disease course.
Conclusions:
- DNA immunization can modulate chronic virus-induced demyelinating disease.
- Targeting specific viral proteins via DNA vaccination may offer potential therapeutic avenues for MS and similar conditions.