A novel recombinant Salmonella vaccine enhances the innate immunity of NK cells against acute myeloid leukaemia cells Kasumi-1 in vitro

Cell Biol Int. 2013 Dec;37(12):1320-9. doi: 10.1002/cbin.10173. Epub 2013 Oct 1.

Abstract

Minor histocompatibility antigen HA-1-specific cytotoxic lymphocyte (CTL) clones have apparent anti-leukaemic efficacy, and the AML/ETO gene is a special fusion gene in leukaemic cells. Thus, we hypothesised that a vaccine targeting HA-1 and AML/ETO could stimulate NK cells to target leukaemia cells. Furthermore, we packaged the vaccine using attenuated Salmonella to enhance its immuno-activity. Expression of the NK cell-activating ligand ULBP2 was notably elevated upon packaging in a co-recombinant group. An AML/ETO single plasmid gave the weakest vaccine. The level of miR-182, which targets ULBP2, significantly decreased with increasing IFN-γ and granzyme B in a co-recombinant group. In summary, DNA vaccines including AML/ETO and HA-1 fragments significantly enhance the innate immunity of NK cells in vitro.

Keywords: DNA vaccine; NK cells; Salmonella; innate immunity.

MeSH terms

  • Apoptosis
  • Bacterial Vaccines / immunology*
  • Cells, Cultured
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Granzymes / metabolism
  • HEK293 Cells
  • Humans
  • Immunity, Innate*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • MicroRNAs / metabolism
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism
  • Oligopeptides / genetics
  • Oligopeptides / metabolism
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism
  • RNA, Messenger / metabolism
  • RUNX1 Translocation Partner 1 Protein
  • Recombinant Fusion Proteins / genetics
  • Salmonella / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Vaccines, DNA / immunology*

Substances

  • Bacterial Vaccines
  • GPI-Linked Proteins
  • HA-1 antigen
  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • Mirn182 microRNA, human
  • Oligopeptides
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RUNX1 Translocation Partner 1 Protein
  • RUNX1T1 protein, human
  • Recombinant Fusion Proteins
  • Transcription Factors
  • ULBP2 protein, human
  • Vaccines, DNA
  • Interferon-gamma
  • Granzymes