title: IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection.
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.
authors.affiliation: Viral-Immunobiology Laboratory, Department of Molecular and Integrative Neuroscience, The Scripps Research Institute, La Jolla, CA 92037, USA. dbrooks@scripps.edu
authors.forename: David G
authors.initials: DG
authors.lastname: Brooks
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Lee
authors.forename: Heidi
authors.initials: H
authors.lastname: Elsaesser
authors.forename: Dorian B
authors.initials: DB
authors.lastname: McGavern
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology* / Q000821:virology; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000037:antagonists & inhibitors*; D008217:Lymphocytic choriomeningitis virus / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D053701:Receptors, Interleukin-10 / Q000037:antagonists & inhibitors; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000494:pharmacology*; D014765:Viral Vaccines / Q000235:genetics / Q000494:pharmacology*
chemical_list: D053701:Receptors, Interleukin-10; D019444:Vaccines, DNA; D014765:Viral Vaccines; D016753:Interleukin-10