Abstract
Hepatitis C virus (HCV) is an important global health concern with approximately 185 million people infected [1]. HCV infection most often leads to chronic infection with few early symptoms, but chronically infected individuals can develop liver cirrhosis and hepatocellular carcinoma. Genome-wide association studies in humans have identified innate associated genes and HLA class II as important predictors of spontaneous clearance of HCV [2,3], but the correlates of protective immunity are not fully defined. The existence of few models to study protective immunity has hindered vaccine development research. Despite this limitation, significant advancements have been made in our understanding of protective immune responses to HCV using the chimpanzee model and humans exposed to HCV (Fig 1). Fig 1 Hepatitis C virus vaccine development has been hindered by few representative models and the recent significant limitation in use of chimpanzees as a model.
Highlights
While recently developed direct-acting antiviral agents (DAAs) cure Hepatitis C virus (HCV) at high rates, several factors may limit their overall impact
Even in the United States, only 50% of people who are infected are aware of their HCV-positive status [5,6], and many of the most at-risk populations, such as people who inject drugs (PWID), infrequently seek medical care
Chronic infection is characterized by the progressive loss of functional HCV-specific T cells, which leads to inability to clear the virus
Summary
HCV leads to chronic infection in 75% of people, while 25% of people are able to spontaneously clear the virus. Humans who have previously cleared a primary infection go on to resolve subsequent infections 83% of the time [14] These individuals have decreased viral titers and more rapid clearance of virus compared to initial infection, suggesting a protective adaptive immune component [14]. Reinfection in humans was associated with broadened cellular response to HCV and an increase in broadly HCV-neutralizing antibodies [14] Taken together, these data support the role of the adaptive immune system in providing protective immune responses to subsequent HCV challenge, and development of a vaccine to elicit similar adaptive responses may confer protective immunity
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