Adaptive Immune Response against Hepatitis C Virus.
A functional adaptive immune response is the major determinant for clearance of hepatitis C virus (HCV) infection. However, in the majority of patients, this response fails and persistent infection evolves. Here, we dissect the HCV-specific key players of adaptive immunity, namely B cells and T cells, and describe factors that affect infection outcome. Once chronic infection is established, continuous exposure to HCV antigens affects functionality, phenotype, transcriptional program, metabolism, and the epigenetics of the adaptive immune cells. In addition, viral escape mutations contribute to the failure of adaptive antiviral immunity. Direct-acting antivirals (DAA) can mediate HCV clearance in almost all patients with chronic HCV infection, however, defects in adaptive immune cell populations remain, only limited functional memory is obtained and reinfection of cured individuals is possible. Thus, to avoid potential reinfection and achieve global elimination of HCV infections, a prophylactic vaccine is needed. Recent vaccine trials could induce HCV-specific immunity but failed to protect from persistent infection. Thus, lessons from natural protection from persistent infection, DAA-mediated cure, and non-protective vaccination trials might lead the way to successful vaccination strategies in the future.
['Kemming|Janine|J|', 'Thimme|Robert|R|', 'Neumann-Haefelin|Christoph|C|0000-0001-7351-1387']
D056704:Adaptive Immunity D000818:Animals D000917:Antibody Formation D002986:Clinical Trials as Topic D016174:Hepacivirus D006801:Humans D013601:T-Lymphocytes D014765:Viral Vaccines
hepatitis C virus B cell T cell viral escape T cell exhaustion neutralizing antibody