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@ARTICLE{Cavazzini:181524,
      author       = {D. Cavazzini and G. Spagnoli and F. C. Mariz$^*$ and F.
                      Reggiani and S. Maggi and V. Franceschi and G. Donofrio and
                      M. Müller$^*$ and A. Bolchi and S. Ottonello},
      title        = {{E}nhanced immunogenicity of a positively supercharged
                      archaeon thioredoxin scaffold as a cell-penetrating antigen
                      carrier for peptide vaccines.},
      journal      = {Frontiers in immunology},
      volume       = {13},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2022-02059},
      pages        = {958123},
      year         = {2022},
      abstract     = {Polycationic resurfaced proteins hold great promise as
                      cell-penetrating bioreagents but their use as carriers for
                      the intracellular delivery of peptide immuno-epitopes has
                      not thus far been explored. Here, we report on the
                      construction and functional characterization of a positively
                      supercharged derivative of Pyrococcus furiosus thioredoxin
                      (PfTrx), a thermally hyperstable protein we have previously
                      validated as a peptide epitope display and immunogenicity
                      enhancing scaffold. Genetic conversion of 13 selected amino
                      acids to lysine residues conferred to PfTrx a net charge of
                      +21 (starting from the -1 charge of the wild-type protein),
                      along with the ability to bind nucleic acids. In its unfused
                      form, +21 PfTrx was readily internalized by HeLa cells and
                      displayed a predominantly cytosolic localization. A
                      different intracellular distribution was observed for a +21
                      PfTrx-eGFP fusion protein, which although still capable of
                      cell penetration was predominantly localized within
                      endosomes. A mixed cytosolic/endosomal partitioning was
                      observed for a +21 PfTrx derivative harboring three tandemly
                      repeated copies of a previously validated HPV16-L2 (aa
                      20-38) B-cell epitope grafted to the display site of
                      thioredoxin. Compared to its wild-type counterpart, the
                      positively supercharged antigen induced a faster immune
                      response and displayed an overall superior immunogenicity,
                      including a substantial degree of self-adjuvancy.
                      Altogether, the present data point to +21 PfTrx as a
                      promising novel carrier for intracellular antigen delivery
                      and the construction of potentiated recombinant subunit
                      vaccines.},
      keywords     = {antigen carrier (Other) / epitope display (Other) /
                      intracellular antigen delivery (Other) / peptide epitope
                      (Other) / protein DNA interaction (Other) / protein scaffold
                      engineering (Other) / protein scaffold vaccine (Other) /
                      recombinant vaccine (Other)},
      cin          = {F035},
      ddc          = {610},
      cid          = {I:(DE-He78)F035-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36032169},
      pmc          = {pmc:PMC9405434},
      doi          = {10.3389/fimmu.2022.958123},
      url          = {https://inrepo02.dkfz.de/record/181524},
}