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CD 8 T‐cell priming upon mRNA vaccination is restricted to bone‐marrow‐derived antigen‐presenting cells and may involve antigen transfer from myocytes
Author(s) -
Lazzaro Sandra,
Giovani Cinzia,
Mangiavacchi Simona,
Magini Diletta,
Maione Domenico,
Baudner Barbara,
Geall Andrew J.,
De Gregorio Ennio,
D'Oro Ugo,
Buonsanti Cecilia
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12505
Subject(s) - priming (agriculture) , antigen presenting cell , antigen , microbiology and biotechnology , biology , t cell , immunology , bone marrow , cytotoxic t cell , cd8 , immune system , in vivo , major histocompatibility complex , in vitro , biochemistry , genetics , botany , germination
Summary Self‐amplifying mRNA s ( 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 ( APC s) 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 APC s rather than muscle cells are responsible for induction of MHC class‐I restricted CD 8 T cells in vivo , but direct transfection of APC s 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 APC s, suggesting cross‐priming as the prevalent mechanism for priming the CD 8 T‐cell response by SAM vaccines.