title: Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection.
abstract: BACKGROUND
  Regulatory T cells (Tregs) have been shown to limit anti-viral immunity during chronic retroviral infection and to restrict vaccine-induced T cell responses. The objective of the study was to assess whether a combinational therapy of nanoparticle-based therapeutic vaccination and concomitant transient ablation of Tregs augments anti-viral immunity and improves virus control in chronically retrovirus-infected mice. Therefore, chronically Friend retrovirus (FV)-infected mice were immunized with calcium phosphate (CaP) nanoparticles functionalized with TLR9 ligand CpG and CD8(+) or CD4(+) T cell epitope peptides (GagL85-93 or Env gp70123-141) of FV. In addition, Tregs were ablated during the immunization process. Reactivation of CD4(+) and CD8(+) effector T cells was analysed and the viral loads were determined.
  
  
  RESULTS
  Therapeutic vaccination of chronically FV-infected mice with functionalized CaP nanoparticles transiently reactivated cytotoxic CD8(+) T cells and significantly reduced the viral loads. Transient ablation of Tregs during nanoparticle-based therapeutic vaccination strongly enhanced anti-viral immunity and further decreased viral burden.
  
  
  CONCLUSIONS
  Our data illustrate a crucial role for CD4(+) Foxp3(+) Tregs in the suppression of anti-viral T cell responses during therapeutic vaccination against chronic retroviral infection. Thus, the combination of transient Treg ablation and therapeutic nanoparticle-based vaccination confers robust and sustained anti-viral immunity.
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Knuschke
authors.affiliation: Institute of Inorganic Chemistry and Center for Nanointegration (CeNIDE), University of Duisburg-Essen, 45141, Essen, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Rotan
authors.affiliation: Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Wibke
authors.initials: W
authors.lastname: Bayer
authors.affiliation: Institute of Inorganic Chemistry and Center for Nanointegration (CeNIDE), University of Duisburg-Essen, 45141, Essen, Germany.
authors.forename: Viktoriya
authors.initials: V
authors.lastname: Sokolova
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Hansen
authors.affiliation: Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Medicine, 30625, Hannover, Germany.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: Institute of Virology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Institute of Inorganic Chemistry and Center for Nanointegration (CeNIDE), University of Duisburg-Essen, 45141, Essen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Epple
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Buer
authors.affiliation: Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, 45122, Essen, Germany. astrid.westendorf@uk-essen.de.
authors.forename: Astrid M
authors.initials: AM
authors.lastname: Westendorf
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003131:Combined Modality Therapy / Q000379:methods; D005622:Friend murine leukemia virus / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology / Q000628:therapy*; D047589:Leukocyte Reduction Procedures; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D012192:Retroviridae Infections / Q000276:immunology / Q000628:therapy*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome; D014412:Tumor Virus Infections / Q000276:immunology / Q000628:therapy*; D014765:Viral Vaccines / Q000008:administration & dosage*
chemical_list: D014765:Viral Vaccines
keywords: Chronic retrovirus infection; Nanoparticles-based vaccine; Regulatory T cells