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Progress in the development of preventive and therapeutic vaccines for hepatitis C virus

Published on Jun 1, 2011in Journal of Hepatology18.95
· DOI :10.1016/j.jhep.2010.09.040
Joseph Torresi39
Estimated H-index: 39
(University of Melbourne),
Douglas F. Johnson14
Estimated H-index: 14
(University of Melbourne),
Heiner Wedemeyer70
Estimated H-index: 70
Cite
Abstract
Hepatitis C virus (HCV) is a blood borne disease estimated to chronically infect 3% of the worlds' population causing significant morbidity and mortality. Current medical therapy is curative in approximately 50% of patients. While recent treatment advances of genotype 1 infection using directly acting antiviral agents (DAAs) are encouraging, there is still a need to develop vaccine strategies capable of preventing infection. Moreover, vaccines may also be used in future in combination with DAAs enabling interferon-free treatment regimens. Viral and host specific factors contribute to viral evasion and present important impediments to vaccine development. Both, innate and adaptive immune responses are of major importance for the control of HCV infection. However, HCV has evolved ways of evading the host's immune response in order to establish persistent infection. For example, HCV inhibits intracellular interferon signalling pathways, impairs the activation of dendritic cells, CD8 + and CD4 + T cell responses, induces a state of T-cell exhaustion and selects escape variants with mutations CD8 + T cell epitopes. An effective vaccine will need to produce strong and broadly cross-reactive CD4 + , CD8 + T cell and neutralising antibody (NAb) responses to be successful in preventing or clearing HCV. Vaccines in clinical trials now include recombinant proteins, synthetic peptides, virosome based vaccines, tarmogens, modified vaccinia Ankara based vaccines, and DNA based vaccines. Several preclinical vaccine strategies are also under development and include recombinant adenoviral vaccines, virus like particles, and synthetic peptide vaccines. This paper will review the vaccines strategies employed, their success to date and future directions of vaccine design.
  • References (157)
  • Citations (108)
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References157
Newest
Published on Sep 1, 2010in Gastroenterology19.23
Harel Dahari10
Estimated H-index: 10
(UIC: University of Illinois at Chicago),
Stephen M. Feinstone58
Estimated H-index: 58
(CBER: Center for Biologics Evaluation and Research),
Marian E. Major22
Estimated H-index: 22
(CBER: Center for Biologics Evaluation and Research)
Background & Aims Studies in patients and chimpanzees that spontaneously cleared hepatitis C virus (HCV) infections demonstrated that natural immunity to the virus is induced during primary infections and that this immunity can be cross protective. These discoveries led to optimism about prophylactic HCV vaccines, and several studies were performed in chimpanzees, although most included fewer than 6 animals. To draw meaningful conclusions about the efficacy of HCV vaccines in chimpanzees, we per...
Published on Apr 1, 2010in Hepatology14.97
Paul Feuerstadt4
Estimated H-index: 4
(Albert Einstein College of Medicine),
Ari L. Bunim1
Estimated H-index: 1
(Albert Einstein College of Medicine)
+ 7 AuthorsJohn F. Reinus16
Estimated H-index: 16
(Albert Einstein College of Medicine)
Randomized controlled trials of hepatitis C virus (HCV) therapy with pegylated interferon and ribavirin have demonstrated sustained viral response rates (SVRs) of 54%-63% (efficacy). Treatment results in clinical practice (effectiveness) may not be equivalent. The goal of this study was to assess the effectiveness of HCV treatment with pegylated interferon and ribavirin in a treatment-naive, human immunodeficiency virus (HIV)-negative, United States urban population with many ethnic minority pat...
Published on Apr 1, 2010in Hepatology14.97
Sophie E. Krieger5
Estimated H-index: 5
(UDS: University of Strasbourg),
Mirjam B. Zeisel37
Estimated H-index: 37
(UDS: University of Strasbourg)
+ 14 AuthorsMélanie Lambotin8
Estimated H-index: 8
(UDS: University of Strasbourg)
The tight junction protein claudin-1 (CLDN1) has been shown to be essential for hepatitis C virus (HCV) entry-the first step of viral infection. Due to the lack of neutralizing anti-CLDN1 antibodies, the role of CLDN1 in the viral entry process is poorly understood. In this study, we produced antibodies directed against the human CLDN1 extracellular loops by genetic immunization and used these antibodies to investigate the mechanistic role of CLDN1 for HCV entry in an infectious HCV cell culture...
Published on Apr 1, 2010in Gastroenterology19.23
Andri Rauch35
Estimated H-index: 35
(University of Bern),
Zoltán Kutalik13
Estimated H-index: 13
(Swiss Institute of Bioinformatics)
+ 24 AuthorsJan Borovicka21
Estimated H-index: 21
(HSG: University of St. Gallen)
Background & Aims Hepatitis C virus (HCV) induces chronic infection in 50% to 80% of infected persons; approximately 50% of these do not respond to therapy. We performed a genome-wide association study to screen for host genetic determinants of HCV persistence and response to therapy. Methods The analysis included 1362 individuals: 1015 with chronic hepatitis C and 347 who spontaneously cleared the virus (448 were coinfected with human immunodeficiency virus [HIV]). Responses to pegylated interf...
Published on Mar 1, 2010in Journal of Immunology4.72
Henry Radziewicz10
Estimated H-index: 10
(Emory University),
Chris C. Ibegbu24
Estimated H-index: 24
(Emory University)
+ 8 AuthorsNaglaa H. Shoukry27
Estimated H-index: 27
(UdeM: Université de Montréal)
Costimulatory signals via B7/CD28 family molecules (signal 2) are critical for effective adaptive CD8 + T cell immune responses. In addition to costimulatory signals, B7/CD28 family coinhibitory receptor/ligands that modulate immune responses have been identified. In acute hepatitis C virus (HCV) infection, programmed death receptor 1, an inhibitory receptor in the CD28 family, is highly expressed on virus-specific CD8 + T cells, yet vigorous immune responses often develop. We hypothesized that ...
Published on Mar 1, 2010in Vaccine3.27
Christa Firbas19
Estimated H-index: 19
(Medical University of Vienna),
Thomas Boehm2
Estimated H-index: 2
(Intercell)
+ 4 AuthorsChristoph Klade19
Estimated H-index: 19
(Intercell)
Abstract Background An effective vaccine would be a significant progress in the management of chronic HCV infections. This study was designed to examine whether different application schedules and injection routes may enhance the immunogenicity of the HCV peptide vaccine IC41. Methods In this randomized trial 54 healthy subjects received either subcutaneous (s.c.) or intradermal (i.d.) vaccinations weekly (16 injections) or every other week (8 injections). One group additionally received imiquim...
Published on Jan 1, 2010in Hepatology14.97
Christoph Neumann-Haefelin24
Estimated H-index: 24
(MIT: Massachusetts Institute of Technology),
Jörg Timm15
Estimated H-index: 15
+ 18 AuthorsDermot Kelleher56
Estimated H-index: 56
Human leukocyte antigen B27 (HLA-B27) is associated with protection in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection. This protective role is linked to single immunodominant HLA-B27-restricted CD8+ T-cell epitopes in both infections. In order to define the relative contribution of a specific HLA-B27-restricted epitope to the natural course of HCV infection, we compared the biological impact of the highly conserved HCV genotype 1 epitope, for which the protective role h...
Published on Oct 1, 2009in Journal of Hepatology18.95
Jason Grebely45
Estimated H-index: 45
(UNSW: University of New South Wales),
David L. Thomas88
Estimated H-index: 88
(Johns Hopkins University),
Gregory J. Dore72
Estimated H-index: 72
(UNSW: University of New South Wales)
Two decades have passed since the discovery of hepatitis C virus (HCV) in 1989 [1]. Despite a massively expanded understanding of the virus and rapidly improving treatments, there is still no effective vaccine to prevent new HCV infections. A central question in HCV vaccine development is whether long-lasting, sustained protective immunity against HCV can be achieved. Multiple chimpanzee and human studies have provided valuable insights into this question. However, depending on the interpretatio...
Cited By108
Newest
Amir Atapour2
Estimated H-index: 2
(Shiraz University of Medical Sciences),
Pooneh Mokaram11
Estimated H-index: 11
(Shiraz University of Medical Sciences)
+ 4 AuthorsNavid Nezafat12
Estimated H-index: 12
(Shiraz University of Medical Sciences)
Hepatitis C virus (HCV) infection is a major global issue that leads to serious liver disease such as chronic liver inflammation and hepatocellular carcinoma. At present, no approved vaccine is available for control or treatment of HCV infection. Therefore, the development of an efficient vaccine against HCV is an urgent need. Today, designing an effective vaccine against hepatitis C is one of the outmost propriety for researchers. Fusion protein vaccines containing the immunogen proteins and ad...
Published on May 24, 2019in Frontiers in Immunology4.72
Makutiro Ghislain Masavuli1
Estimated H-index: 1
,
Danushka K. Wijesundara9
Estimated H-index: 9
+ 6 AuthorsBranka Grubor-Bauk7
Estimated H-index: 7
Hepatitis C virus (HCV) persistently infects approximately 71 million people globally. To prevent infection a vaccine which elicits neutralizing antibodies against the virus envelope proteins (E1/E2) which are required for entry into host cells is desirable. DNA vaccines are cost-effective to manufacture globally and despite recent landmark studies highlighting the therapeutic efficacy of DNA vaccines in humans against cervical cancer, DNA vaccines encoding E1/E2 developed thus far are poorly im...
Published on Oct 2, 2018in British Journal of Biomedical Science2.37
Mahmoud El-Bendary6
Estimated H-index: 6
(Mansoura University),
Mustafa Neamatallah3
Estimated H-index: 3
(Mansoura University)
+ 11 AuthorsA Gomaa1
Estimated H-index: 1
ABSTRACTBackground: Single nucleotide polymorphisms (SNPs) of Toll-like receptors (TLRs) are linked with functional modification of cytokine responses. In chronic hepatitis C virus (HCV) infection, studies of TLR polymorphisms have primarily targeted receptor pathways implicated in viral immune responses. We hypothesized that one or more variant(s) of TLR3, TLR7 and TLR8 are associated with different outcomes of HCV infection.Materials & methods: A total of 3368 subjects from 850 families were r...
Xuan Guo1
Estimated H-index: 1
,
Jin-yi Zhong1
Estimated H-index: 1
,
Jun-wen Li1
Estimated H-index: 1
In the twenty-seven years since the discovery of hepatitis C virus (HCV) the majority of individuals exposed to HCV establish a persistent infection, which is a leading cause of chronic liver disease, cirrhosis and hepatocellular carcinoma. In developed nations, the cure rates of HCV infection could be over 90% with direct-acting antiviral (DAA) regimens, which has made the great progress in global eradication. However, the cost of these treatments is so expensive that the patients in developing...
Published on Dec 1, 2017in Scientific Reports4.01
Nazrul Islam9
Estimated H-index: 9
(Harvard University),
Mel Krajden43
Estimated H-index: 43
(UBC: University of British Columbia)
+ 5 AuthorsNaveed Z. Janjua25
Estimated H-index: 25
(UBC: University of British Columbia)
While about a quarter of individuals clear their primary hepatitis C (HCV) infections spontaneously, clearance (spontaneous or treatment-induced) does not confer sterilizing immunity against a future infection. Since successful treatment does not prevent future infections either, an effective vaccine is highly desirable in preventing HCV (re)infection. However, development of an effective vaccine has been complicated by the diversity of HCV genotypes, and complexities in HCV immunological respon...
Published on Dec 1, 2017in Plant Biotechnology Journal6.84
Jihong Liu Clarke8
Estimated H-index: 8
,
Lisa Paruch2
Estimated H-index: 2
+ 15 AuthorsYanliang Wang5
Estimated H-index: 5
Summary The hepatitis C virus (HCV) is a major etiologic agent for severe liver diseases (e.g., cirrhosis, fibrosis and hepatocellular carcinoma). Approximately 140 million people have chronic HCV infections and about 500,000 die yearly from HCV-related liver pathologies. To date, there is no licenced vaccine available to prevent HCV infection and production of an HCV vaccine remains a major challenge. Here we report the successful production of the HCV E1E2 heterodimer, an important vaccine can...
Published on Jul 1, 2017in International Immunopharmacology3.36
Kiandokht Borhani1
Estimated H-index: 1
(TMU: Tarbiat Modares University),
Taravat Bamdad11
Estimated H-index: 11
(TMU: Tarbiat Modares University),
Tayebeh Hashempour4
Estimated H-index: 4
(Shiraz University of Medical Sciences)
Abstract Hepatitis C virus (HCV) is a blood-borne pathogen which has chronically infected people worldwide. Therefore, it is of utmost importance to design prophylactic and therapeutic vaccine in order to control HCV infection. To date, several researchers have attempted to improve the efficiency of HCV vaccine by using different adjuvants. However, a few studies have focused on the synthetic immunomodulatory drugs as adjuvants for HCV vaccine. Recently, researchers have shown that lenalidomide,...
Published on May 1, 2017in Journal of General Virology2.81
Soma Das7
Estimated H-index: 7
(IISc: Indian Institute of Science),
Ranajoy Mullick5
Estimated H-index: 5
(IISc: Indian Institute of Science)
+ 10 AuthorsNarayanaswamy Srinivasan39
Estimated H-index: 39
(IISc: Indian Institute of Science)
Hepatitis C virus (HCV) is a leading cause of chronic viral hepatitis, but an effective vaccine is still not available to prevent infection. Use of neutralizing antibodies could be a potential therapeutic option. In this study, the presence of anti-HCV antibodies in HCV-infected patients was assessed from 50 patients and the presence of neutralizing antibodies was examined using `hepatitis C virus-like particles'. Antibodies from two samples exhibited significant inhibitory activity, suggesting ...
Published on Apr 1, 2017in Viral Immunology1.42
Abstract We previously generated an oral hepatitis C virus (HCV) vaccine using Bifidobacterium displaying the HCV nonstructural protein 3 (NS3) polypeptide. NS3-specific cellular immunity is important for viral clearance and recovery from HCV infection. In this study, we enhanced the cellular immune responses induced by our oral HCV vaccine, Bifidobacterium longum 2165 (B. longum 2165), by combining interferon-α (IFN-α) as an adjuvant with the vaccine in a mouse experimental model. IFN-α is a wi...
Published on Jan 1, 2017
Ashraf A. Tabll13
Estimated H-index: 13
,
Reem El-Shenawy3
Estimated H-index: 3
,
Yasmine S. El Abd4
Estimated H-index: 4
View next paperVaccination of chimpanzees against infection by the hepatitis C virus.