An Endogenous Immune Adjuvant Released by Necrotic Cells for Enhancement of DNA Vaccine Potency

Document Type: Original Article

Authors

1 Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran

2 Department of Microbiology, Tehran Medical Branch, Islamic Azad University, Tehran, Iran

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.
Method: 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).
Conclusion: The supernatant of necrotic cells contains adjuvant properties that can be considered as a candidate for tumor vaccination.

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