title: An endogenous immune adjuvant released by necrotic cells for enhancement of DNA vaccine potency.
abstract: BACKGROUND
  Improving vaccine potency in the induction of a strong cell-mediated cytotoxicity can enhance the efficacy of vaccines. Necrotic cells and the supernatant of necrotic tumor cells are attractive adjuvants, on account of their ability to recruit antigen-presenting cells to the site of antigen synthesis as well as its ability to stimulate the maturation of dendritic cells.
  
  
  OBJECTIVE
  To evaluate the utility of supernatant of necrotic tumor cells as a DNA vaccine adjuvant in a murine model.
  
  
  METHODS
  The supernatant of EL4 necrotic cells was co-administered with a DNA vaccine expressing the glycoprotein B of Herpes simplex virus-1 as an antigen model under the control of Cytomegalovirus promoter. C57BL/6 mice were vaccinated three times at two weeks intervals with glycoprotein B DNA vaccine and supernatant of necrotic EL4 cells. Five days after the last immunization, cell cytotoxicity, IFN-γ and IL-4 were evaluated.
  
  
  RESULTS
  The obtained data showed that the production of IFN-γ from the splenocytes after antigenic stimulation in the presence of the supernatant of necrotic EL4 cells was significantly higher than the other groups (p<0.002). The flow cytometry results showed a significant increase in the apoptosis/necrosis of EL4 cells in the mice immunized with DNA vaccine and supernatant of necrotic EL4 cells comparing to the other groups (p<0.001).
  
  
  CONCLUSIONS
  The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.
authors.affiliation: Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran,  e-mail: Bamdad_T@modares.ac.ir.
authors.forename: Rohollah
authors.initials: R
authors.lastname: Dorostkar
authors.forename: Taravat
authors.initials: T
authors.lastname: Bamdad
authors.forename: Masoud
authors.initials: M
authors.lastname: Parsania
authors.forename: Hassan
authors.initials: H
authors.lastname: Pouriayevali
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008223:Lymphoma / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009336:Necrosis / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000235:genetics; D019444:Vaccines, DNA / Q000276:immunology* / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C562160:glycoprotein B, human herpesvirus 1; D015847:Interleukin-4; D007371:Interferon-gamma