Abstract

Hepatitis C Virus (HCV) infects 2% of the world’s population and is the leading cause of liver disease and liver transplantation. It poses a serious and growing worldwide public health problem that will only be partially addressed with the introduction of new antiviral therapies. However, these treatments will not prevent re-infection particularly in high risk populations. The introduction of a HCV vaccine has been predicted, using simulation models in a high risk population, to have a significant effect on reducing the incidence of HCV. A vaccine with 50 to 80% efficacy targeted to high-risk intravenous drug users could dramatically reduce HCV incidence in this population. Virus like particles (VLPs) are composed of viral structural proteins which self-assemble into non-infectious particles that lack genetic material and resemble native viruses. Thus, VLPs represent a safe and highly immunogenic vaccine delivery platform able to induce potent adaptive immune responses. Currently, many VLP-based vaccines have entered clinical trials, while licensed VLP vaccines for hepatitis B virus (HBV) and human papilloma virus (HPV) have been in use for many years. The HCV core, E1 and E2 proteins can self-assemble into immunogenic VLPs while inclusion of HCV antigens into heterogenous (chimeric) VLPs is also a promising approach. These VLPs are produced using different expression systems such as bacterial, yeast, mammalian, plant, or insect cells. Here, this paper will review HCV VLP-based vaccines and their immunogenicity in animal models as well as the different expression systems used in their production.

Highlights

  • Hepatitis C Virus is an enveloped positive sense single-stranded RNA virus that infects more than 170 million people (∼2% of the world’s population) (Bartenschlager et al, 2011)

  • It is estimated that approximately ∼1% of those diagnosed with hepatitis C virus infection are treated annually in Australia (Commonwealth of Australia, 2014), while the global pool of Hepatitis C Virus (HCV) infected persons is increased by 3–4 million new infections each year (Gower et al, 2014)

  • Attempts should be directed toward the optimization of the delivery methods of DNA-based Virus like particles (VLPs) vaccines and the addition or co-delivery of novel genetic adjuvants for maximum immune stimulation. These results show that the plasmo-retroVLPs is a flexible platform to induce humoral and cellular immunity after homologous or heterologous prime-boost immunization and with further improvements, this strategy could be used as a Recombinant Papaya Mosaic Virus-Based HCV VLPs

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Summary

INTRODUCTION

Hepatitis C Virus is an enveloped positive sense single-stranded RNA virus that infects more than 170 million people (∼2% of the world’s population) (Bartenschlager et al, 2011). Hepatitis C Virus-LPs that were produced in mammalian cells using an adenovirus-based system generated particles which were reported to resemble the native virions morphologically (Chua et al, 2012; Kumar et al, 2016) Vaccination with these adenovirus-derived HCV-LPs in combination with an anionic self-adjuvanting lipopeptide containing the Toll-like receptor (TLR) 2 agonist Pam2Cys (E8Pam2Cys) resulted in significant HCV-LP and E2-specific antibody responses mice (Chua et al, 2012). Vaccination of human leukocyte antigen (HLA)-A2 transgenic mice with this vaccine generated higher HCV-LP-specific IFN-γ-mediated responses compared to non-adjuvanted HCV-LPs (Chua et al, 2012)

Mice Mice and macaques Mice Mice
Mice Mice Mice Mice
Mammalian cells Plant cells
Recombinant Vesicular Stomatitis Virus Vectors Expressing HCV VLPs
HCV VLP PRODUCTION SYSTEMS
Bacteria and Yeast
Mammalian Cells
Plant Cells
Insect Cells
DOWNSTREAM PROCESSING OF VLP VACCINES
Findings
CONCLUSION
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