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

The immunogenicity of DNA vaccines is enhanced by CpG motifs present in the plasmid backbone, which can activate APC via toll like receptors (TLR9) [32] [33] [34] . Unmethylated CpG motifs have been reported to induce B cell proliferation and secretion of immunoglobulin in vitro and in vivo [33] . Activation of macrophages and DCs results in upregulation of antigen presentation and costimulatory molecules, and secretion of cytokines (IL-12 and IL-18) involved in helper T cells (Th1) response [34] . Thus, CpG motifs in DNA plasmids serve as a 'natural adjuvant' for DNA vaccines. Plasmid DNA can be designed to encode additional adjuvants with the antigen(s) of interest. Molecular adjuvants such as fusion proteins including heat shock protein 70 (HSP70), and vesicular stomatitis virus (VSVG) have been developed and used to enhance vaccine immunogenicity [35] [36] [37] . The gene encoding such proteins as adjuvants is either fused with the gene encoding the vaccine antigen to produce a fusion protein driven by a same promoter or as separate proteins driven by different promoters in the same or different plasmid. Co-encoding of genes creates a suitable cellular micro environment such as sustained antigen release and/or upregulation of cytokines, enhancing the immunogenicity of DNA vaccines [38] .