Protective antibody responses against HCV E1E2 in high-risk populations

Hepatitis C is a global health problem with an estimate of 71 million chronically infected people worldwide in 2015. To reduce the global burden of hepatitis C virus (HCV), a new generation of treatments were developed. Despite the high efficacy of the therapies, the HCV epidemic continues to expand worldwide. Therefore, a vaccine against HCV is urgently needed. In order to design an effective vaccine, it is necessary to understand immune protection against this virus. It is well established that antibodies play critical roles in the immune response against viruses. However, little is known about the role of antibodies in spontaneous clearance of HCV infection and protection upon re-exposure. Therefore, we studied the antibody response specific for the HCV glycoproteins E1 and E2 in individuals protected against chronic HCV infection.
Our main finding is that a high frequency of B cells expressing cross-genotype specific antibodies was associated with spontaneous clearance of one or multiple infections. Interestingly, the cross-genotype specific antibodies were mainly directed against a particular epitope on E2, called AR3, and exhibited cross-neutralizing activity against different HCV genotypes. Moreover, we demonstrated that 25 years after clearance, AR3-specific B cells could be detected indicating that this antibody response can be long-lasting. Finally, we studied antibody responses in plasma of HCV individuals coinfected with human immunodeficiency virus (HIV). Although these individuals were HIV co-infected, some individuals could develop a broadly neutralizing antibody response against HCV during acute infection.
These observations should form the basis for developing an efficacious HCV vaccine.