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

Different recombinant cytolytic DNA-PRF vaccines (rDNA-PRF) have been shown to elicit immune responses higher than those elicited by canonical DNA vaccines (without PRF) and the mechanism underlying this has been established [94] . A previous study showed that coexpression of HCV NS3 and PRF elicited nonapoptotic cell death in transfected cells, whilst immunization with NS3-PRF DNA vaccine increased NS3-specific T cell mediated responses as evidenced by increased NS3-specific IFN-γ responses in an ELISpot assay and increased numbers of polyfunctional CD8 + T EM cells that simultaneously secreted IFN-γ, IL-2, and TNF-α [56] . Cytolytic DNA platform where the expression of immunogen is driven by a stronger promoter allows for sufficient antigen expression and accumulation within the target cells followed by nonapoptotic cell death due to lesser expression of PRF driven by a weaker SV40 promoter; thus, balancing the level of antigen expression with the timing of cell death [94] .