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Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up

Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and...

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Autores principales: Hartlage, Alex S., Kapoor, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402855/
https://www.ncbi.nlm.nih.gov/pubmed/34452460
http://dx.doi.org/10.3390/v13081596
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author Hartlage, Alex S.
Kapoor, Amit
author_facet Hartlage, Alex S.
Kapoor, Amit
author_sort Hartlage, Alex S.
collection PubMed
description Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and lastly, the evaluation of selected vaccines in human clinical trials. The recently concluded first phase II clinical trial of a human hepatitis C virus (HCV) vaccine followed this approach. Still, despite promising preclinical results, it failed to protect against chronic infection, raising grave concerns about our understanding of protective immunity. This setback, combined with the lack of HCV animal models and availability of new highly effective antivirals, has fueled ongoing discussions of using a controlled human infection model (CHIM) to test new HCV vaccine candidates. Before taking on such an approach, however, we must carefully weigh all the ethical and health consequences of human infection in the absence of a complete understanding of HCV immunity and pathogenesis. We know that there are significant gaps in our knowledge of adaptive immunity necessary to prevent chronic HCV infection. This review discusses our current understanding of HCV immunity and the critical gaps that should be filled before embarking upon new HCV vaccine trials. We discuss the importance of T cells, neutralizing antibodies, and HCV genetic diversity. We address if and how the animal HCV-like viruses can be used for conceptualizing effective HCV vaccines and what we have learned so far from these HCV surrogates. Finally, we propose a logical but narrow path forward for HCV vaccine development.
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spelling pubmed-84028552021-08-29 Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up Hartlage, Alex S. Kapoor, Amit Viruses Review Unless urgently needed to prevent a pandemic, the development of a viral vaccine should follow a rigorous scientific approach. Each vaccine candidate should be designed considering the in-depth knowledge of protective immunity, followed by preclinical studies to assess immunogenicity and safety, and lastly, the evaluation of selected vaccines in human clinical trials. The recently concluded first phase II clinical trial of a human hepatitis C virus (HCV) vaccine followed this approach. Still, despite promising preclinical results, it failed to protect against chronic infection, raising grave concerns about our understanding of protective immunity. This setback, combined with the lack of HCV animal models and availability of new highly effective antivirals, has fueled ongoing discussions of using a controlled human infection model (CHIM) to test new HCV vaccine candidates. Before taking on such an approach, however, we must carefully weigh all the ethical and health consequences of human infection in the absence of a complete understanding of HCV immunity and pathogenesis. We know that there are significant gaps in our knowledge of adaptive immunity necessary to prevent chronic HCV infection. This review discusses our current understanding of HCV immunity and the critical gaps that should be filled before embarking upon new HCV vaccine trials. We discuss the importance of T cells, neutralizing antibodies, and HCV genetic diversity. We address if and how the animal HCV-like viruses can be used for conceptualizing effective HCV vaccines and what we have learned so far from these HCV surrogates. Finally, we propose a logical but narrow path forward for HCV vaccine development. MDPI 2021-08-12 /pmc/articles/PMC8402855/ /pubmed/34452460 http://dx.doi.org/10.3390/v13081596 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Hartlage, Alex S.
Kapoor, Amit
Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title_full Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title_fullStr Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title_full_unstemmed Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title_short Hepatitis C Virus Vaccine Research: Time to Put Up or Shut Up
title_sort hepatitis c virus vaccine research: time to put up or shut up
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402855/
https://www.ncbi.nlm.nih.gov/pubmed/34452460
http://dx.doi.org/10.3390/v13081596
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