title: The recombinant tuberculosis vaccine rBCG ΔureC::hly(+) induces apoptotic vesicles for improved priming of CD4(+) and CD8(+) T cells.
abstract: BACKGROUND
  The recombinant BCG ΔureC::hly(+) (rBCG) vaccine candidate is more efficient than parental BCG (pBCG) against tuberculosis (TB) in preclinical models. Evidence exists for superior CD4 and CD8 T cell stimulation. Although the responsible immune mechanisms are incompletely understood, crosspriming of CD8 T cells has been proposed as a major mechanism underlying better protection of rBCG over pBCG. The present study investigates the role of apoptotic vesicles from pBCG- and rBCG-infected macrophages in crosspriming.
  
  
  METHODS
  Apoptotic vesicles were isolated from pBCG- and rBCG-infected mouse macrophages. The priming potential of the isolated vesicles was evaluated in terms of dendritic cell activation and specific T cell stimulation.
  
  
  RESULTS
  Apoptotic vesicles from both pBCG- and rBCG-infected macrophages activated dendritic cells but to a different degree. Overall, rBCG-infected apoptotic vesicles induced more profound CD4 and CD8 T cell responses as compared to pBCG.
  
  
  CONCLUSIONS
  These data support the notion that the improved vaccine efficacy of rBCG rests on enhanced crosspriming as a consequence of stronger apoptosis.
authors.affiliation: Max Planck Institute for Infection Biology, Department of Immunology, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Maura
authors.initials: M
authors.lastname: Farinacci
authors.forename: Stephan
authors.initials: S
authors.lastname: Weber
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000818:Animals; D017209:Apoptosis; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D022162:Cytoplasmic Vesicles / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D017353:Gene Deletion; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016254:Mutagenesis, Insertional; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001500:BCG Vaccine; D014614:Vaccines, Synthetic