Abstract |
Therapeutic vaccination is a potentially powerful strategy to establish immune control and eradicate persistent viral infections. Large and multifunctional antiviral T cell responses are associated with control of viral persistence; however, for reasons that were mostly unclear, current therapeutic vaccination approaches to restore T cell immunity and control viral infection have been ineffective. Herein, we confirmed that neutralization of the immunosuppressive factor interleukin (IL)-10 stimulated T cell responses and improved control of established persistent lymphocytic choriomeningitis virus (LCMV) infection. Importantly, blockade of IL-10 also allowed an otherwise ineffective therapeutic DNA vaccine to further stimulate antiviral immunity, thereby increasing T cell responses and enhancing clearance of persistent LCMV replication. We therefore propose that a reason that current therapeutic vaccination strategies fail to resurrect/sustain T cell responses is because they do not alleviate the immunosuppressive environment. Consequently, blocking key suppressive factors could render ineffective vaccines more efficient at improving T cell immunity, and thereby allow immune-mediated control of persistent viral infection.
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Authors | David G Brooks, Andrew M Lee, Heidi Elsaesser, Dorian B McGavern, Michael B A Oldstone |
Journal | The Journal of experimental medicine
(J Exp Med)
Vol. 205
Issue 3
Pg. 533-41
(Mar 17 2008)
ISSN: 1540-9538 [Electronic] United States |
PMID | 18332180
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Receptors, Interleukin-10
- Vaccines, DNA
- Viral Vaccines
- Interleukin-10
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Topics |
- Animals
- Arenaviridae Infections
(immunology, virology)
- Immunosuppression Therapy
- Interleukin-10
(antagonists & inhibitors)
- Lymphocytic choriomeningitis virus
(genetics, immunology)
- Mice
- Mice, Inbred C57BL
- Mice, Transgenic
- Receptors, Interleukin-10
(antagonists & inhibitors)
- T-Lymphocytes
(immunology, virology)
- Vaccination
- Vaccines, DNA
(genetics, pharmacology)
- Viral Vaccines
(genetics, pharmacology)
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