Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Nov;2(11):e79.
doi: 10.1038/emi.2013.79. Epub 2013 Nov 20.

Progress towards a hepatitis C virus vaccine

Lok Man John Law  1 , Abdolamir Landi  1 , Wendy C Magee  1 , D Lorne Tyrrell  1 , Michael Houghton  1
Affiliations
Review

Progress towards a hepatitis C virus vaccine

Lok Man John Law et al. Emerg Microbes Infect. 2013 Nov.

Abstract

New drugs to treat hepatitis C are expected to be approved over the next few years which promise to cure nearly all patients. However, due to issues of expected drug resistance, suboptimal activity against diverse hepatitis C virus (HCV) genotypes and especially because of their extremely high cost, it is unlikely that these HCV drugs will substantially reduce the world's HCV carrier population of around 170 million in the near future or the estimated global incidence of millions of new HCV infections. For these reasons, there is an urgent need to develop a prophylactic HCV vaccine and also to determine if therapeutic vaccines can aid in the treatment of chronically infected patients. After much early pessimism on the prospects for an effective prophylactic HCV vaccine, our recent knowledge of immune correlates of protection combined with the demonstrated immunogenicity and protective animal efficacies of various HCV vaccine candidates now allows for realistic optimism. This review summarizes the current rationale and status of clinical and experimental HCV vaccine candidates based on the elicitation of cross-neutralizing antibodies and broad cellular immune responses to this highly diverse virus.

Keywords: HCV; hepatitis; infection; prophylactic; therapeutic; vaccine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Summary of selected potential HCV vaccines in clinical development. These vaccines were grouped based on either prophylactic or therapeutic usage. They are currently either in phase I, phase I/II or phase II development (no HCV-specific vaccine has reached phase III development yet). The biological component(s) of the vaccine is listed on top of the arrow. Sponsor or company conducting the trial is listed at the end of arrow along with clinical ID number (http://www.clinicaltrials.gov). Selected examples of vaccines will be further discussed in the text. NIAID, National Institute of Allergy and Infectious Diseases.
Figure 2
Figure 2
Neutralizing antibodies in patients with resolved or chronic hepatitis C. Anti-HCVpp neutralizing titers were determined by end point dilution of sera. HCVpp or control pp were pre-incubated for 1 h with serial serum dilutions before infection of Huh7 target cells. The end point titers of the early phase (1–6 months after infection) and late-phase (10–17 years after infection) serum samples are shown as scatter plots. The median titer is marked by a line. Data are expressed as means of two independent experiments performed in duplicate. Samples showing a titer of <1/20 were considered negative. The cutoff titer 1/20 is indicated by a dashed line. The data are reproduced with permission from Pestka et al. HCVpp, HCV pseudo-particles.
Figure 3
Figure 3
Proliferative CD4+ T-cell response of the first sample in the acute phase of disease to recombinant HCV proteins (HCV-NS3, -NS4, -NS5 and -core) of PBMCs from 38 patients with acute hepatitis C. Patients are grouped according to the final outcome of disease in self-limited hepatitis C (SL, n=20) and patients with chronic evolution (C, n=18). Results are shown as SI=3H-thymidine incorporation of antigen-stimulated PBMCs (counts per minute)/unstimulated control. All patients with self-limited disease displayed a significant proliferative T-cell response against at least one of the viral proteins, while patients with chronic evolution mounted no or only transient antiviral T-cell responses. NS3 and NS4 revealed the most frequent and most vigorous responses. In four patients, the proliferative response against NS5 was not tested in the first sample. The data are reproduced with permission from Gerlach et al. PBMC, peripheral blood mononucleated cell; SI, simulation index.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989;244:359–362. - PubMed
    1. Ciesek S, Manns MP. Hepatitis in 2010: the dawn of a new era in HCV therapy. Nat Rev Gastroenterol Hepatol. 2011;8:69–71. - PubMed
    1. Chatel-Chaix L, Germain MA, Gotte M, Lamarre D. Direct-acting and host-targeting HCV inhibitors: current and future directions. Curr Opin Virol. 2012;2:588–598. - PubMed
    1. Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41:1105–1109. - PubMed
    1. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461:399–401. - PubMed