Progress in the development of vaccines for hepatitis C virus infection

Abstract

The hepatitis C virus (HCV), first described in 1989, is now a leading cause of liver cirrhosis and hepatocellular carcinoma. With more than 170 million people infected globally, this virus is a major public health issue. The current standard therapy is based on interferon in combination with ribavirin. This costly therapy often fails to completely clear the infection and is associated with adverse side effects. Recent anti-HCV therapies are interferon-free direct-acting antiviral (DAA) regimens for HCV, including simeprevir, sofosbuvir, and ledipasvir, which have effects on non-structural proteins. DAA regimens have several advantages, such as specifically targeting HCV viral replication, accompanied by very high sustained virological response rates and lower side effects like flu-like syndrome. These facts plus the fact that most HCV cases progress to chronic infection suggest the potential need for an efficient HCV vaccine. Different innovative methods, including methods based on peptide, recombinant protein, DNA, vector-based, and virus-like particles, have been introduced for the development of HCV vaccines. An extensive number of studies have been published on these vaccines, and some vaccines were even tested in clinical trials. In the current review, progress in the development of preventive and therapeutic vaccines against the HCV is reviewed in the context of peptide vaccines, recombinant protein vaccines, HCV-like particle, DNA vaccines and viral vectors expressing HCV genes.

Keywords: Hepatitis C virus; Hepatitis C virus infection; Preventive vaccine; Therapeutic vaccine.

Figure 1

Summary of immune responses against hepatitis C virus. In innate immune response, NK cells are activated, which leads to the production of IFNs 1-11. This would inhibit the production of viral particles and destroy their genomes. In addition, in normal cells, antiviral effects are mediated through inhibition of protein synthesis. Adaptive immune responses work through the activation of T cells and production of cytokines that result in inhibition of the growth of the virus and elimination of the infected cells. B cells perform their actions through the production of neutralizing antibodies against the virus. Ab: Antibody; BCR: B cell receptor; CTL: cytotoxic T lymphocyte; E1: HCV E1 glycoprotein; E2: HCV E2 glycoprotein; GZ: Granzyme; HCV: Hepatitis C virus; IL: Interleukin; IFN: Interferon; mDC: Myeloid dendritic cell; NK cell: Natural killer cell; pDC: Plasmoid dendritic cell; Th: T helper cell; TGF: Transforming growth factor; TNF: Tumor necrosis factor.