Special Issue "Novel Advances in Vaccines against HCV"

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 March 2021).

Special Issue Editor

Prof. Thomas Fuerst
E-Mail Website
Guest Editor
Director, Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Professor, Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, MD 20742, USA
Interests: virology; vaccines; adaptive immunity, immunoadjuvants; delivery systems; virus assembly and maturation; hepatitis C virus; emerging and re-emerging viruses

Special Issue Information

Dear Colleagues,

Hepatitis C virus (HCV) is a major global disease burden, and the leading cause of liver cirrhosis and hepatocellular carcinoma in those infected. Despite the recent approval of antiviral therapeutics, a preventative vaccine is recognized as the most effective means to control HCV globally, particularly in at-risk and developing country populations.

However, there are major challenges in the development of an effective HCV vaccine. These challenges include high sequence variability across the seven major genotypes and subtypes leading to viral evasion of both innate and adaptive immune responses, lack of in vitro systems and immunocompetent small animal models that facilitate determination of protective immunity, and vaccine immunoadjuvant and delivery systems capable of inducing robust humoral and cellular immune responses. It is generally accepted that an effective vaccine will need to produce strong and broadly cross-reactive neutralizing antibodies (bNAbs) and HCV-specific T cell responses (CD4+ and CD8+) to prevent or clear HCV infection. Approaches to elicit humoral immunity have focused on the envelope glycoproteins, E1 and E2, with a principal focus on the E1E2 heterodimer to induce bNAbs. Protective immunity against autologous virus challenge has been demonstrated in chimpanzees immunized with an E1E2-based vaccine, and limited success with heterologous challenge strains. Corresponding human studies have shown moderate immunogenicity with limited cross-neutralization across genotypes. Therefore, the design of the envelope glycoproteins to focus the immune response on conserved domains associated with broadly neutralizing antibodies is an active area of investigation. In addition, the generation of effective cellular and T-cell memory responses will be necessary for protective immunity and control of HCV infection. Therefore, the use of novel adjuvant and delivery systems for the induction of humoral and cellular responses will be of key importance.

This Special Issue will focus on existing vaccines in development, and recent novel advances in developing B and T cell-based vaccines. This, coupled with insights from deep sequencing, surrogate neutralization assays, and animal model systems, and other technological advances, is advancing research toward rationally designed vaccines that preferentially elicit responses toward conserved epitopes of interest that are associated with viral neutralization and clearance.

Prof. Thomas Fuerst
Guest Editor

Manuscript Submission Information

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Keywords

  • Hepatitis C virus
  • B cell response
  • T cell response
  • neutralization antibodies
  • human monoclonal antibodies
  • viral escape
  • epitope mapping
  • antigenic domains
  • vaccine development
  • immunoadjuvants
  • vector delivery systems.

Published Papers (4 papers)

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Research

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Open AccessArticle
Design and Synthesis of HCV-E2 Glycoprotein Epitope Mimics in Molecular Construction of Potential Synthetic Vaccines
Viruses 2021, 13(2), 326; https://doi.org/10.3390/v13020326 - 20 Feb 2021
Cited by 1 | Viewed by 374
Abstract
Hepatitis C virus remains a global threat, despite the availability of highly effective direct-acting antiviral (DAA) drugs. With thousands of new infections annually, the need for a prophylactic vaccine is evident. However, traditional vaccine design has been unable to provide effective vaccines so [...] Read more.
Hepatitis C virus remains a global threat, despite the availability of highly effective direct-acting antiviral (DAA) drugs. With thousands of new infections annually, the need for a prophylactic vaccine is evident. However, traditional vaccine design has been unable to provide effective vaccines so far. Therefore, alternative strategies need to be investigated. In this work, a chemistry-based approach is explored towards fully synthetic peptide-based vaccines using epitope mimicry, by focusing on highly effective and conserved amino acid sequences in HCV, which, upon antibody binding, inhibit its bio-activity. Continuous and discontinuous epitope mimics were both chemically synthesized based on the HCV-E2 glycoprotein while using designed fully synthetic cyclic peptides. These cyclic epitope mimics were assembled on an orthogonally protected scaffold. The scaffolded epitope mimics have been assessed in immunization experiments to investigate the elicitation of anti-HCV-E2 glycoprotein antibodies. The neutralizing potential of the elicited antibodies was investigated, representing a first step in employing chemically synthesized epitope mimics as a novel strategy towards vaccine design. Full article
(This article belongs to the Special Issue Novel Advances in Vaccines against HCV)
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Review

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Open AccessReview
Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
Viruses 2021, 13(5), 837; https://doi.org/10.3390/v13050837 - 05 May 2021
Viewed by 252
Abstract
A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic [...] Read more.
A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune evasion. Structure-based and rational vaccine design approaches have capitalized on insights regarding the immune response to HCV and the structures of antibody-bound envelope glycoproteins. Despite successes with other viruses, designing an immunogen based on HCV glycoproteins that can elicit broadly protective immunity against HCV infection is an ongoing challenge. Here, we describe HCV vaccine design approaches where immunogens were selected and optimized through analysis of available structures, identification of conserved epitopes targeted by neutralizing antibodies, or both. Several designs have elicited immune responses against HCV in vivo, revealing correlates of HCV antigen immunogenicity and breadth of induced responses. Recent studies have elucidated the functional, dynamic and immunological features of key regions of the viral envelope glycoproteins, which can inform next-generation immunogen design efforts. These insights and design strategies represent promising pathways to HCV vaccine development, which can be further informed by successful immunogen designs generated for other viruses. Full article
(This article belongs to the Special Issue Novel Advances in Vaccines against HCV)
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Open AccessReview
From Structural Studies to HCV Vaccine Design
Viruses 2021, 13(5), 833; https://doi.org/10.3390/v13050833 - 04 May 2021
Viewed by 290
Abstract
Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an effective cross-genotype vaccine is needed. The failure of previous vaccination trials to elicit an effective cross-reactive immune response [...] Read more.
Hepatitis C virus (HCV) is a serious and growing public health problem despite recent developments of antiviral therapeutics. To achieve global elimination of HCV, an effective cross-genotype vaccine is needed. The failure of previous vaccination trials to elicit an effective cross-reactive immune response demands better vaccine antigens to induce a potent cross-neutralizing response to improve vaccine efficacy. HCV E1 and E2 envelope (Env) glycoproteins are the main targets for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. Therefore, a molecular-level understanding of the nAb responses against HCV is imperative for the rational design of cross-genotype vaccine antigens. Here we summarize the recent advances in structural studies of HCV Env and Env-nAb complexes and how they improve our understanding of immune recognition of HCV. We review the structural data defining HCV neutralization epitopes and conformational plasticity of the Env proteins, and the knowledge applicable to rational vaccine design. Full article
(This article belongs to the Special Issue Novel Advances in Vaccines against HCV)
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Open AccessReview
To Include or Occlude: Rational Engineering of HCV Vaccines for Humoral Immunity
Viruses 2021, 13(5), 805; https://doi.org/10.3390/v13050805 - 30 Apr 2021
Viewed by 249
Abstract
Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines [...] Read more.
Direct-acting antiviral agents have proven highly effective at treating existing hepatitis C infections but despite their availability most countries will not reach the World Health Organization targets for elimination of HCV by 2030. A prophylactic vaccine remains a high priority. Whilst early vaccines focused largely on generating T cell immunity, attention is now aimed at vaccines that generate humoral immunity, either alone or in combination with T cell-based vaccines. High-resolution structures of hepatitis C viral glycoproteins and their interaction with monoclonal antibodies isolated from both cleared and chronically infected people, together with advances in vaccine technologies, provide new avenues for vaccine development. Full article
(This article belongs to the Special Issue Novel Advances in Vaccines against HCV)
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