Hepatitis C virus (HCV) is a global health threat and a leading cause of liver cancer, responsible for nearly 0.3 million deaths each year. In the USA, chronic HCV infection is the primary cause of liver cancer, yet no vaccine exists to prevent it. While antiviral drugs can cure HCV, they do not provide lasting immunity or prevent reinfection. Developing HCV vaccine is challenging due to virus’s extensive genetic diversity and high mutation rate, creating genetically diverse strains that evade the immune system. Traditional vaccine approaches fail because they generate strain-specific immunity rather than broad protection against diverse HCV variants. Additionally, the immune system is often misdirected to recognize ineffective viral targets on HCV, producing antibodies that cannot neutralize the virus. However, research has shown that approximately 25% individuals infected with HCV naturally develop highly potent antibodies capable of neutralizing multiple HCV strains. These antibodies target conserved regions of the virus that are essential for infection and survival, making them ideal targets for vaccine development. This project aims to develop vaccine candidates that mimics this natural immunity. Using advanced computational modeling and protein design, I will create a two-step vaccine that first trains the immune system to recognize effective viral targets, and then strengthens this response to ensure broad protection. We will test the vaccine in preclinical mouse models to evaluate its ability to generate protective antibodies against diverse HCV strains. If successful, this research could lay the foundation for a much-needed preventive vaccine against HCV and its associated cancers.