Cancer and chronic viral infections share similarities in persisting and evading the immune system. Immunotherapy including immune checkpoint blockade, adoptive cell therapies, and cancer vaccines, demonstrated promising clinical responses. Nevertheless, the urgent need for effective vaccines remains, particularly for hepatitis C virus (HCV), a significant global health issue linked to liver cancer. Despite the success of direct-acting antivirals (DAAs), challenges like accessibility and reinfection risk persist, highlighting the need for vaccines.
This thesis of Georgia Koutsoumpli aimed at developing therapeutic vaccines against HCV, enhancing efficacy through antigen modifications, and exploring methodologies for selecting optimal antigens for HCV and cancer vaccines. Utilizing the potent alphavirus vector SFV, our findings showed induction of strong cellular immune responses against HCV antigens conserved across different genotypes and improved vaccine immunogenicity, under suboptimal immunization conditions, through vector modifications. An in vitro priming assay using cultures of PBMCs and an unbiased analysis of the antigenic landscape of HCV infection allowed the identification of functional epitopes truly presented by infected hepatocytes for inclusion in a vaccine candidate. Overall, our findings support the rational design of therapeutic vaccines targeting HCV and a range of other pathogens and cancer antigens.
