2015/07/14 by Sandra Lazzaro, Cinzia Giovani, Simona Mangiavacchi +9 · 4 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Immune Cell Function and Interaction #Immunotherapy and Immune Responses #RNA Interference and Gene Delivery
paper · pdf · doi:10.1111/imm.12505
openalex publication_date 2015/07/14 · crossref created 2015/07/14 · crossref issued 2015/08/28 · crossref published 2015/08/28 · crossref published-online 2015/08/28 · crossref published-print 2015/10/01 · openalex created_date 2016/06/24 · crossref deposited 2023/10/01 · crossref indexed 2026/07/30 · openalex updated_date 2026/07/31
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.