Hepatitis C Virus Infection and Vaccine Development

Guo, Xuan; Zhong, Jin-Yi; Lǐ, Jùnwén

doi:10.1016/j.jceh.2018.02.003

Cited by 20 publications

(15 citation statements)

References 99 publications

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“…History and modeling suggest that HCV eradication will necessitate a vaccine. Progress in the understanding of the immune response to HCV has led to different vaccinal strategies, including DNA, peptides or recombinant proteins, vector-based vaccines, and virus-like particles or dendritic cell-based vaccination strategies; these are at various levels of development (recently reviewed in [158]). The challenge is to develop a vaccine eliciting both a broad T-cell response and neutralizing antibodies against a highly variable virus hidden in lipoviroparticles.…”

Section: Discussionmentioning

confidence: 99%

Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Alazard-Dany

Denolly

Boson

et al. 2019

Viruses

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Hepatitis C infection is the leading cause of liver diseases worldwide and a major health concern that affects an estimated 3% of the global population. Novel therapies available since 2014 and 2017 are very efficient and the WHO considers HCV eradication possible by the year 2030. These treatments are based on the so-called direct acting antivirals (DAAs) that have been developed through research efforts by academia and industry since the 1990s. After a brief overview of the HCV life cycle, we describe here the functions of the different targets of current DAAs, the mode of action of these DAAs and potential future inhibitors.

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Section: Discussionmentioning

confidence: 99%

Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Alazard-Dany

Denolly

Boson

et al. 2019

Viruses

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“…This is likely to improve the adaptive immunity in these patients but not to the same level of improvement observed with DAA-associated reestablishment of innate immunity homeostasis [221]. A DAA-mediated cure of HCV is associated with the normalization of innate immunity with a partial restoration of exhausted HCV-specific CD8 + T cells that express low levels of PD-1 [222].…”

Section: Impact Of Host–hcv Interactions On Hcv Therapymentioning

confidence: 99%

Hepatitis C Virus Infection: Host–Virus Interaction and Mechanisms of Viral Persistence

Chigbu

Loonawat

Sehgal

et al. 2019

Cells

118

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Hepatitis C (HCV) is a major cause of liver disease, in which a third of individuals with chronic HCV infections may develop liver cirrhosis. In a chronic HCV infection, host immune factors along with the actions of HCV proteins that promote viral persistence and dysregulation of the immune system have an impact on immunopathogenesis of HCV-induced hepatitis. The genome of HCV encodes a single polyprotein, which is translated and processed into structural and nonstructural proteins. These HCV proteins are the target of the innate and adaptive immune system of the host. Retinoic acid-inducible gene-I (RIG-I)-like receptors and Toll-like receptors are the main pattern recognition receptors that recognize HCV pathogen-associated molecular patterns. This interaction results in a downstream cascade that generates antiviral cytokines including interferons. The cytolysis of HCV-infected hepatocytes is mediated by perforin and granzyme B secreted by cytotoxic T lymphocyte (CTL) and natural killer (NK) cells, whereas noncytolytic HCV clearance is mediated by interferon gamma (IFN-γ) secreted by CTL and NK cells. A host–HCV interaction determines whether the acute phase of an HCV infection will undergo complete resolution or progress to the development of viral persistence with a consequential progression to chronic HCV infection. Furthermore, these host–HCV interactions could pose a challenge to developing an HCV vaccine. This review will focus on the role of the innate and adaptive immunity in HCV infection, the failure of the immune response to clear an HCV infection, and the factors that promote viral persistence.

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“…The accumulating structural information on HCV glycoproteins suggest that the design of suitable immunogens will be key for success. So far, several types of B-cell vaccine strategies have been explored in combination with adjuvants including recombinant E1E2, E1 and E2 glycoproteins, DNA vaccines expressing these envelope proteins, chimeric HBV-HCV envelope proteins and virus-like particles (VLPs) [ 111 , 112 , 113 , 114 , 115 ]. Administration of a subunit vaccine consisting of the CHO-cell expressed E1E2 glycoproteins from genotype 1a elicited a human antibody response mainly directed against the HVR1 and was rather isolate-specific [ 12 , 62 ].…”

Section: Implications For a Structure-based Design Of A B Cell Vacmentioning

confidence: 99%

HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development

Stroh

Krey

2020

IJMS

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Despite the approval of highly efficient direct-acting antivirals in the last decade Hepatitis C virus (HCV) remains a global health burden and the development of a vaccine would constitute an important step towards the control of HCV. The high genetic variability of the viral glycoproteins E1 and E2, which carry the main neutralizing determinants, together with their intrinsic structural flexibility, the high level of glycosylation that shields conserved neutralization epitopes and immune evasion using decoy epitopes renders the design of an efficient vaccine challenging. Recent structural and functional analyses have highlighted the role of the CD81 receptor binding site on E2, which overlaps with those neutralization epitopes within E2 that have been structurally characterized to date. This CD81 binding site consists of three distinct segments including “epitope I”, “epitope II” and the “CD81 binding loop”. In this review we summarize the structural features of the HCV glycoproteins that have been derived from X-ray structures of neutralizing and non-neutralizing antibody fragments complexed with either recombinant E2 or epitope-derived linear peptides. We focus on the current understanding how neutralizing antibodies interact with their cognate antigen, the structural features of the respective neutralization epitopes targeted by nAbs and discuss the implications for informed vaccine design.

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Hepatitis C Virus Infection and Vaccine Development

Cited by 20 publications

References 99 publications

Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Overview of HCV Life Cycle with a Special Focus on Current and Possible Future Antiviral Targets

Hepatitis C Virus Infection: Host–Virus Interaction and Mechanisms of Viral Persistence

HCV Glycoprotein Structure and Implications for B-Cell Vaccine Development

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