Combination of nanoparticle-based therapeutic vaccination and transient ablation of regulatory T cells enhances anti-viral immunity during chronic retroviral infection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-04-14

AUTHORS

Torben Knuschke, Olga Rotan, Wibke Bayer, Viktoriya Sokolova, Wiebke Hansen, Tim Sparwasser, Ulf Dittmer, Matthias Epple, Jan Buer, Astrid M. Westendorf

ABSTRACT

BackgroundRegulatory 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.ResultsTherapeutic 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.ConclusionOur 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. More... »

PAGES

24

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12977-016-0258-9

DOI

http://dx.doi.org/10.1186/s12977-016-0258-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1033996396

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27076190


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