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

VSV G is a type III viral fusion envelope protein, which mediates fusion of the virus envelope and the host cell membrane [86] . The use of fusogenic membrane glycoprotein (FMG) gene from VSV in a DNA vaccine encoding the H7 protein of human papillomavirus type 16 was shown to enhance CD8 + T cell responses and effectively control growth of tumors [87] . The VSV G protein was also shown to induce a T-response at low doses or a T-independent response at higher doses [88] . FMG fuses cells into large multinucleated syncytia, which are then killed by a nonapoptotic mechanism [89] . Syncytiosomes are released from the membrane and present antigens efficiently to DCs [90] . FMGs can thus act as an adjuvant for any antigen expressed by a DNA vaccine. Vaccination of mice with the hepatitis C virus (HCV) nonstructural protein 3 (NS3) together with VSVG resulted in increased frequency of IFN-γ, but not TNF-α-or IL-2-producing CD3+ CD44+ CD8+ effector memory T (T EM ) cells [57] . This DNA vaccine was constructed in a bicistronic vector with VSVG co-encoded in the same plasmid with HCV NS3. VSVG expression was driven by a weaker SV40 promoter and NS3 by a stronger CMV promoter [57] . However, others have also reported an increase in the specific CMI when the immunogen and VSVG were expressed from different plasmids [37, 87] .