DNA-based vaccines: The future of multiple sclerosis therapy?

Research output: Contribution to journalReview article

Olaf Stüve, Petra D. Cravens, Todd N. Eagar

Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have antiinflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFN? production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS.

Original languageEnglish (US)
Pages (from-to)351-360
Number of pages10
JournalExpert Review of Neurotherapeutics
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2008

PMID: 18345967

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DNA-based vaccines : The future of multiple sclerosis therapy? / Stüve, Olaf; Cravens, Petra D.; Eagar, Todd N.

In: Expert Review of Neurotherapeutics, Vol. 8, No. 3, 01.03.2008, p. 351-360.

Research output: Contribution to journalReview article

Harvard

Stüve, O, Cravens, PD & Eagar, TN 2008, 'DNA-based vaccines: The future of multiple sclerosis therapy?' Expert Review of Neurotherapeutics, vol. 8, no. 3, pp. 351-360. https://doi.org/10.1586/14737175.8.3.351

APA

Stüve, O., Cravens, P. D., & Eagar, T. N. (2008). DNA-based vaccines: The future of multiple sclerosis therapy? Expert Review of Neurotherapeutics, 8(3), 351-360. https://doi.org/10.1586/14737175.8.3.351

Vancouver

Stüve O, Cravens PD, Eagar TN. DNA-based vaccines: The future of multiple sclerosis therapy? Expert Review of Neurotherapeutics. 2008 Mar 1;8(3):351-360. https://doi.org/10.1586/14737175.8.3.351

Author

Stüve, Olaf ; Cravens, Petra D. ; Eagar, Todd N. / DNA-based vaccines : The future of multiple sclerosis therapy?. In: Expert Review of Neurotherapeutics. 2008 ; Vol. 8, No. 3. pp. 351-360.

BibTeX

@article{6ae0eb0c45e54280ac8c9778c2cb4dea,
title = "DNA-based vaccines: The future of multiple sclerosis therapy?",
abstract = "Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have antiinflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFN? production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS.",
keywords = "Autoimmune disease, Bystander suppression, Clinical trial, DNA, Deoxyribonucleic acid, EAE, Experimental autoimmune encephalomyelitis, Immunization, MS, Multiple sclerosis, Pharmacotherapy, Therapy, Tolerance, Treatment, Vaccine",
author = "Olaf St{\"u}ve and Cravens, {Petra D.} and Eagar, {Todd N.}",
year = "2008",
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pages = "351--360",
journal = "Expert Review of Neurotherapeutics",
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}

RIS

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T1 - DNA-based vaccines

T2 - Expert Review of Neurotherapeutics

AU - Stüve, Olaf

AU - Cravens, Petra D.

AU - Eagar, Todd N.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have antiinflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFN? production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS.

AB - Multiple sclerosis (MS) is the most common human inflammatory, demyelinating and degenerative disorder of the CNS. Based mostly on work in experimental autoimmune encephalomyelitis, CD4+ T cells were long thought to play the crucial role in MS pathogenesis. Only more recently has it been recognized that other effector cell types, including CD8+ T cells, γδ-T cells and B lymphocytes may also have an important role in disease initiation and perpetuation. The expression of soluble inflammatory mediators, including cytokines and free radicals, may be one of the late pathways mediating CNS tissue damage. In addition, in virtually all patients with MS, an oligoclonal banding pattern of antibodies can be detected in the cerebrospinal fluid (CSF). However, the cause of MS still remains unknown. Specifically, no single foreign or self antigen has been identified to account for clinical disease activity or the presence of surrogate disease markers. All approved pharmacotherapies have antiinflammatory or immunoregulatory properties and work in early stages of the disease. In a recent clinical trial, BHT-3009, a DNA vaccine encoding full-length human myelin basic protein, was tested in patient with MS. BHT-3009 was safe and well tolerated. In addition, immunization with BHT-3009 induced anti-inflammatory antigen-specific immune changes consisting of a marked decrease in T-cell proliferation of IFN? production and a reduction in titers of myelin-specific autoantibodies in the CSF. This review will discuss these intriguing observations and the overall potential of DNA vaccination in MS.

KW - Autoimmune disease

KW - Bystander suppression

KW - Clinical trial

KW - DNA

KW - Deoxyribonucleic acid

KW - EAE

KW - Experimental autoimmune encephalomyelitis

KW - Immunization

KW - MS

KW - Multiple sclerosis

KW - Pharmacotherapy

KW - Therapy

KW - Tolerance

KW - Treatment

KW - Vaccine

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U2 - 10.1586/14737175.8.3.351

DO - 10.1586/14737175.8.3.351

M3 - Review article

VL - 8

SP - 351

EP - 360

JO - Expert Review of Neurotherapeutics

JF - Expert Review of Neurotherapeutics

SN - 1473-7175

IS - 3

ER -

ID: 16839861