Abstract
The incidence of hepatitis C virus (HCV) infections remains high even more than 10 years after approval of the first direct-acting antivirals for treatment of hepatitis C. In some countries, more people are newly infected with the virus than patients cured by antiviral therapy. The development of a prophylactic vaccine could prevent virus transmission and thereby make a significant contribution to control the global burden of this disease. In this article, we review the unique challenges and current approaches to HCV vaccine development.HCV is a highly diverse and versatile virus that mostly escapes the immune system and establishes chronic infections. However, up to one third of the exposed individuals can spontaneously resolve HCV infections, which indicates that protective immunity can be achieved. Numerous studies on determinants of protective immunity against HCV show an increasingly complete picture of what a vaccine must achieve. It is very likely that both strong neutralizing antibodies and powerful cytotoxic T cells are needed to reliably protect against chronic HCV infection. The key question is which approaches allow maturation of particularly broadly effective antibodies and T cells. This will be necessary to protect against the high number of different HCV variants. The recent successes of mRNA vaccines open new doors for HCV vaccine research and development. Combined with a deeper understanding of the structure and function of the viral envelope proteins, the identification of cross-protective antibody and T‑cell epitopes as well as the use of standardized methods to quantify the effectiveness of vaccine candidates, new perspectives arise for the development of a vaccine.