*2.4. Viral Fusion Protein*

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<sup>+</sup> 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 (TEM) 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].
