Prophylactic vaccines for the hepatitis C virus

Abstract

With the advent of oral, interferon-sparing HCV regimens, it has become much easier to safely and effectively treat HCV infection. However, HCV eradication is not likely to be achieved with treatment alone. Identification of those with HCV infection is challenging, therapies are too costly for countries with the highest incidence, reinfection can occur following treatment, transmission of drug-resistant HCV is possible, and treatment does not fully reverse severe liver damage even when cure is achieved. There is a rising epidemic of acute HCV infection in adolescents and young adults that gives new urgency to prophylactic vaccine development efforts. However, numerous challenges for vaccine development remain, including limited populations in which candidate vaccines can be tested, the enormous sequence diversity of HCV, and incomplete understanding of what mediates protective immunity. The study of immune responses to HCV has provided important insight into protective immunity. However, more research is needed to identify clear correlates of immunity to assess before candidate vaccines are tested in the limited at-risk populations available. Multiple candidate HCV vaccines that induce robust immune responses have been tested in rodents. Fewer have been tested in chimpanzees, with minimal ability to generate sterilizing immunity and variable capacity to prevent persistent infection. A vaccine that was highly immunogenic in healthy volunteers is now being tested in at-risk subjects. The combination of effective antiviral agents to treat HCV infection and a vaccine to prevent persistent infection provide our best chance of substantially reducing morbidity and mortality from HCV on a global scale.