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CD8 T-cell priming upon mRNA vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes.
Lazzaro, Sandra; Giovani, Cinzia; Mangiavacchi, Simona; Magini, Diletta; Maione, Domenico; Baudner, Barbara; Geall, Andrew J; De Gregorio, Ennio; D'Oro, Ugo; Buonsanti, Cecilia.
Afiliação
  • Lazzaro S; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Giovani C; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Mangiavacchi S; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Magini D; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Maione D; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Baudner B; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Geall AJ; GSK Vaccines, Cambridge, MA, USA.
  • De Gregorio E; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • D'Oro U; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
  • Buonsanti C; Novartis Vaccines and Diagnostics s.r.l (a GSK Company), Siena, Italy.
Immunology ; 146(2): 312-26, 2015 Oct.
Article em En | MEDLINE | ID: mdl-26173587
ABSTRACT
Self-amplifying mRNAs (SAM(®) ) are a novel class of nucleic acid vaccines, delivered by a non-viral delivery system. They are effective at eliciting potent and protective immune responses and are being developed as a platform technology with potential to be used for a broad range of targets. However, their mechanism of action has not been fully elucidated. To date, no evidence of in vivo transduction of professional antigen-presenting cells (APCs) by SAM vector has been reported, while the antigen expression has been shown to occur mostly in the muscle fibres. Here we show that bone-marrow-derived APCs rather than muscle cells are responsible for induction of MHC class-I restricted CD8 T cells in vivo, but direct transfection of APCs by SAM vectors is not required. Based on all our in vivo and in vitro data we propose that upon SAM vaccination the antigen is expressed within muscle cells and then transferred to APCs, suggesting cross-priming as the prevalent mechanism for priming the CD8 T-cell response by SAM vaccines.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / RNA Viral / Células da Medula Óssea / Vacinas contra Influenza / Proteínas do Core Viral / Proteínas de Ligação a RNA / Fibras Musculares Esqueléticas / Linfócitos T CD8-Positivos / Apresentação Cruzada / Vírus da Influenza A Subtipo H1N1 Limite: Animals Idioma: En Revista: Immunology Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: RNA Mensageiro / RNA Viral / Células da Medula Óssea / Vacinas contra Influenza / Proteínas do Core Viral / Proteínas de Ligação a RNA / Fibras Musculares Esqueléticas / Linfócitos T CD8-Positivos / Apresentação Cruzada / Vírus da Influenza A Subtipo H1N1 Limite: Animals Idioma: En Revista: Immunology Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Itália