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World J Hepatol. Oct 27, 2021; 13(10): 1234-1268
Published online Oct 27, 2021. doi: 10.4254/wjh.v13.i10.1234
In the era of rapid mRNA-based vaccines: Why is there no effective hepatitis C virus vaccine yet?
Natalia Echeverría, Victoria Comas, Fabián Aldunate, Paula Perbolianachis, Pilar Moreno, Juan Cristina
Natalia Echeverría, Fabián Aldunate, Paula Perbolianachis, Pilar Moreno, Juan Cristina, Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo 11400, Uruguay
Natalia Echeverría, Fabián Aldunate, Paula Perbolianachis, Pilar Moreno, Laboratorio de Evolución Experimental de Virus, Institut Pasteur, Montevideo 11400, Uruguay
Victoria Comas, Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo 11600, Uruguay
Author contributions: Echeverría N contributed to bibliographical revision, article conception, design and drafting, and figure design; Comas V made contributions to article drafting; Perbolianachis P and Aldunate F contributed to bibliographical revision and made revisions related to draft and content; Moreno P and Cristina J made substantial contributions to conception and design, article drafting and revision of intellectual content; all authors contributed to final approval of the version to be published.
Supported by Programa de Desarrollo de las Ciencias Básicas (PEDECIBA); Comisión Académica de Posgrados, Universidad de la República Uruguay (UdelaR); and Comisión Sectorial de Investigación Científica (CSIC, I+D Project ID288).
Conflict-of-interest statement: Dr. Echeverría reports grants from Comisión Sectorial de Investigación Científica (CSIC) and from Comisión Académica de Posgrados (CAP). Dr Echeverría, Dr. Cristina and Dr. Moreno report personal research funding from PEDECIBA. MSc Comas, MSc Aldunate and MSc Perbolianachis declare no conflict of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Juan Cristina, PhD, Full Professor, Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Mataojo 2055, Montevideo 11400, Uruguay. cristina@cin.edu.uy
Received: March 4, 2021
Peer-review started: March 4, 2021
First decision: May 2, 2021
Revised: May 14, 2021
Accepted: September 10, 2021
Article in press: September 10, 2021
Published online: October 27, 2021
Processing time: 231 Days and 15.9 Hours
Abstract

Hepatitis C virus (HCV) is responsible for no less than 71 million people chronically infected and is one of the most frequent indications for liver transplantation worldwide. Despite direct-acting antiviral therapies fuel optimism in controlling HCV infections, there are several obstacles regarding treatment accessibility and reinfection continues to remain a possibility. Indeed, the majority of new HCV infections in developed countries occur in people who inject drugs and are more plausible to get reinfected. To achieve global epidemic control of this virus the development of an effective prophylactic or therapeutic vaccine becomes a must. The coronavirus disease 19 (COVID-19) pandemic led to auspicious vaccine development against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus, which has renewed interest on fighting HCV epidemic with vaccination. The aim of this review is to highlight the current situation of HCV vaccine candidates designed to prevent and/or to reduce HCV infectious cases and their complications. We will emphasize on some of the crossroads encountered during vaccine development against this insidious virus, together with some key aspects of HCV immunology which have, so far, hampered the progress in this area. The main focus will be on nucleic acid-based as well as recombinant viral vector-based vaccine candidates as the most novel vaccine approaches, some of which have been recently and successfully employed for SARS-CoV-2 vaccines. Finally, some ideas will be presented on which methods to explore for the design of live-attenuated vaccines against HCV.

Keywords: Hepatitis C virus; Vaccine candidates; Nucleic acid-based vaccines; Recombinant vector-based vaccines; Challenges; COVID-19

Core Tip: Hepatitis C virus (HCV) remains a global health burden despite the successful introduction of direct-acting antiviral therapies. In order to achieve global control of HCV epidemic a vaccine is necessary. Its development has faced many hurdles, reason why it is still elusive. Herein, we describe all the challenges during HCV vaccine research, focusing on HCV immunology and emphasizing on current vaccine candidates, particularly nucleic acid-based as well as recombinant vector-based vaccines. We also highlight the impact of severe acute respiratory syndrome coronavirus-2 vaccine race on the renewed interest on HCV vaccine production. Finally, we present ideas on live-attenuated vaccine approaches against HCV.