CD8 T-cell priming upon mRNA vaccination is restricted to bone-marrow-derived antigen-presenting cells and may involve antigen transfer from myocytes

Immunology. 2015 Oct;146(2):312-26. doi: 10.1111/imm.12505. Epub 2015 Aug 28.


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.

Keywords: antigen-presenting cells; cross-presentation; muscle cells; nucleic-acid-based vaccines; self-amplifying mRNA.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / virology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / virology
  • Bone Marrow Transplantation
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Cell Communication
  • Cell Line
  • Cricetinae
  • Cross-Priming*
  • Female
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Influenza A Virus, H1N1 Subtype / genetics
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Influenza Vaccines / genetics
  • Influenza Vaccines / immunology*
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muscle Fibers, Skeletal / immunology*
  • Muscle Fibers, Skeletal / virology
  • Nucleocapsid Proteins
  • RNA, Messenger / genetics
  • RNA, Messenger / immunology*
  • RNA, Viral / genetics
  • RNA, Viral / immunology*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology*
  • Transfection
  • Transplantation Chimera
  • Viral Core Proteins / genetics
  • Viral Core Proteins / immunology*


  • Histocompatibility Antigens Class I
  • Influenza Vaccines
  • NP protein, Influenza A virus
  • Nucleocapsid Proteins
  • RNA, Messenger
  • RNA, Viral
  • RNA-Binding Proteins
  • Viral Core Proteins