Reciprocal Inhibition of Immunogenic Performance in Mice of Two Potent DNA Immunogens Targeting HCV-Related Liver Cancer

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, partially reverse disease, but they cannot cure HCV-related cancer. A possible remedy could be multi-component immunotherapeutic vaccine targeting both HCV-infected malignant cells, also those not infected with HCV. To meet this need we developed two-component DNA based highly conserved core protein of to target renowned tumor-associated antigen telomerase transcriptase (TERT) rat TERT, cells. Their synthetic genes were expression-optimized, was truncated after aa 152 (Core152opt) delete domain interfering immunogenicity. Core152opt TERT immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response CD4+ CD8+ T Additionally, DNA-immunization enhanced cellular immune against luciferase encoded by co-delivered plasmid (Luc DNA). However, mix resulted abrogation components. loss bioluminescence signal co-delivery Luc into mice indicated that affects vivo expression directed immediate early cytomegalovirus interferon-β promoters. Panel mutant variants created tested for their effects. deleted N-terminal nucleoli localization mutations abrogating activity still suppressed IFN-β driven expression, while inactivated its analogue, enzymatically active HIV-1 transcriptase, exerted only weak suppressive effects, implying suppression relied presence full-length/nearly full-length enzymatic activity. The effect(s) due interference ectopically expressed xenogeneic biogenesis mRNA, ribosomes translation murine affecting immunogens. can aggravate effect, leading apoptosis co-expressing preventing induction response.