A Novel Adeno-Associated Virus-Based Genetic Vaccine Encoding the Hepatitis C Virus NS3/4 Protein Exhibits Immunogenic Properties in Mice Superior to Those of an NS3-Protein-Based Vaccine.

Fengqin Zhu,Linshan Zhao,Gang Li,Hong Cao,Tian Chen,Haixia Sun,Yeqiong Zhang,Jianxi Lu,R Jude Samulski

doi:10.1371/journal.pone.0142349

Fengqin Zhu, Linshan Zhao + Show 7 more

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https://doi.org/10.1371/journal.pone.0142349

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Abstract

More than 170 million individuals worldwide are infected with hepatitis C virus (HCV), and up to an estimated 30% of chronically infected individuals will go on to develop progressive liver disease. Despite the recent advances in antiviral treatment of HCV infection, it remains a major public health problem. Thus, development of an effective vaccine is urgently required. In this study, we constructed novel adeno-associated virus (AAV) vectors expressing the full-length NS3 or NS3/4 protein of HCV genotype 1b. The expression of the NS3 or NS3/4 protein in HepG2 cells was confirmed by western blotting. C57BL/6 mice were intramuscularly immunised with a single injection of AAV vectors, and the resultant immune response was investigated. The AAV2/rh32.33.NS3/4 vaccine induced stronger humoral and cellular responses than did the AAV2/rh32.33.NS3 vaccine. Our results demonstrate that AAV-based vaccines exhibit considerable potential for the development of an effective anti-HCV vaccine.

Highlights

Hepatitis C virus (HCV) infection is a major public health problem affecting more than 170 million people worldwide and is a leading cause of cirrhosis, hepatocellular carcinoma, and liver failure [1]
NS3 and NS3/4 protein expression after associated virus (AAV) virus infection of HepG2 cells was confirmed by western blotting
The majority of viral vector vaccines against HCV tested to date have been based on adenovirus and the modified vaccinia Ankara virus, both of which provide several advantages because of their efficiency of infection of several cell types [36]

Summary

Introduction

Hepatitis C virus (HCV) infection is a major public health problem affecting more than 170 million people worldwide and is a leading cause of cirrhosis, hepatocellular carcinoma, and liver failure [1]. Treatment for HCV has progressed rapidly, especially for genotype 1. The standard treatment for HCV genotype 1 infection is peginterferon plus ribavirin, with a SVR rate of less than 50%. From 2011, combination of the protease inhibitor with peginterferon and ribavirin increased the sustained virological response (SVR) rates to 70% for untreated HCV genotype 1 infection [2, 3]. Since 2014, the interferon-free regimen of ledipasvir/sofosbuvir (Harvoni,Gilead Sciences) resulted in more than 95% SVR rates in patients with.

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