Cytolytic Perforin as an Adjuvant to Enhance the Immunogenicity of DNA Vaccines

Shrestha, Ashish C.; Wijesundara, Danushka K.; Masavuli, Makutiro G.; Mekonnen, Zelalem A.; Gowans, Eric J.; Grubor-Bauk, Branka

When purified DCs including the CD8α + subset from naïve C57BL/6 mice were exposed to HEK293T cells (transfected with Ovalbumin-PRF), it resulted in upregulation of costimulatory molecules (CD80/CD86), indicating maturation of the immune cells with the cytolytic DNA [94] . A significant increase in CD11c + DCs and cross-presenting CD8a + DCs, and upregulation of CD80 has been reported in mice vaccinated with a cytolytic DNA HIV 1 Gag PRF compared to a canonical DNA vaccine [55] . Local and migrated DCs at the site of inflammation can take up antigens by endocytosis and are also exposed to DAMPs. Activated and matured DCs can then prime naïve CD8 + T cells (Figure 2) . Antigen cross-presentation by DCs to CD8 + T cells has been shown to increase the number of proliferating CD8 + T cells by~2-fold with cytolytic DNA compared to the noncytolytic PRF DNA [94] . Thus, a cytolytic DNA vaccine has an inbuilt adjuvant to enhance the immunogenicity of the vaccine immunogen. Whereas, the immunogenicity of canonical DNA vaccines mostly depends on direct transfection of DCs and to a lesser extent cross-presentation of antigens shed from transfected cells and/or derived from transfected cells that have undergone spontaneous cell death [94] .