State of the Art, Unresolved Issues, and Future Research Directions in the Fight against Hepatitis C Virus: Perspectives for Screening, Diagnostics of Resistances, and Immunization

Abstract

Hepatitis C virus (HCV) still represents a major public health threat, with a dramatic burden from both epidemiological and clinical points of view. New generation of direct-acting antiviral agents (DAAs) has been recently introduced in clinical practice promising to cure HCV and to overcome the issues related to the interferon-based therapies. However, the emergence of drug resistance and the suboptimal activity of DAAs therapies against diverse HCV genotypes have been observed, determining treatment failure and hampering an effective control of HCV spread worldwide. Moreover, these treatments remain poorly accessible, particularly in low-income countries. Finally, effective screening strategy is crucial to early identifying and treating all HCV chronically infected patients. For all these reasons, even though new drugs may contribute to impacting HCV spread worldwide a preventive HCV vaccine remains a cornerstone in the road to significantly reduce the HCV spread globally, with the ultimate goal of its eradication. Advances in molecular vaccinology, together with a strong financial, political, and societal support, will enable reaching this fundamental success in the coming years. In this comprehensive review, the state of the art about these major topics in the fight against HCV and the future of research in these fields are discussed.

Hepatitis C Virus Infection in Egypt: Current Situation and Future Perspective

“…To date, several approaches have been adopted in the development and production of HCV therapeutic vaccines including peptide vaccines, recombinant protein vaccines, DNA vaccines with different carriers, and virally vectored vaccines. (63) -Application of DAAs in children.…”

Hepatitis C virus infection in children and adolescents

“…A preventative vaccine is needed to stop HCV transmission to uninfected individuals and to those who are cured with DAA but remain at risk for re‐exposure and persistence of infection 5. Major obstacles to HCV vaccine development are the diversity of the virus, the ability of the virus to evade the immune response in infected individuals with high rates of mutation, and development of “quasispecies,” which are distinct but closely related HCV variants that can be present in a single individual 5, 137, 142. Additional immune‐evading strategies that have been identified include antibody avoidance, cytotoxic T lymphocyte escape, and a failure to initiate an appropriate T cell response during the beginning of infection, among others 143, 144, 145, 146, 147, 148.…”

Hepatitis C Vaccine Development in the Era of Direct‐Acting Antivirals

“…The potential for achieving this goal is evident from the observation that individuals who have spontaneously cleared the virus are at a substantially reduced risk for persistent infection on reexposure . Variability within the host is believed to stem from the lack of proofreading function of the NS5B RNA‐dependent polymerase, which results in a high error rate per replication cycle and the development of variants known as quasispecies . Other mechanisms through which HCV evades an effective host immune response include immunogenic decoy epitopes that direct the immune response away from effective targets, epitope shielding (such as by nonneutralizing antibodies), major histocompatibility complex downregulation, and direct cell‐to‐cell transmission …”