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Structure-Based and Rational Design of a Hepatitis C Virus Vaccine

A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune...

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Autores principales: Guest, Johnathan D., Pierce, Brian G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148096/
https://www.ncbi.nlm.nih.gov/pubmed/34063143
http://dx.doi.org/10.3390/v13050837
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author Guest, Johnathan D.
Pierce, Brian G.
author_facet Guest, Johnathan D.
Pierce, Brian G.
author_sort Guest, Johnathan D.
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description A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune evasion. Structure-based and rational vaccine design approaches have capitalized on insights regarding the immune response to HCV and the structures of antibody-bound envelope glycoproteins. Despite successes with other viruses, designing an immunogen based on HCV glycoproteins that can elicit broadly protective immunity against HCV infection is an ongoing challenge. Here, we describe HCV vaccine design approaches where immunogens were selected and optimized through analysis of available structures, identification of conserved epitopes targeted by neutralizing antibodies, or both. Several designs have elicited immune responses against HCV in vivo, revealing correlates of HCV antigen immunogenicity and breadth of induced responses. Recent studies have elucidated the functional, dynamic and immunological features of key regions of the viral envelope glycoproteins, which can inform next-generation immunogen design efforts. These insights and design strategies represent promising pathways to HCV vaccine development, which can be further informed by successful immunogen designs generated for other viruses.
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spelling pubmed-81480962021-05-26 Structure-Based and Rational Design of a Hepatitis C Virus Vaccine Guest, Johnathan D. Pierce, Brian G. Viruses Review A hepatitis C virus (HCV) vaccine is a critical yet unfulfilled step in addressing the global disease burden of HCV. While decades of research have led to numerous clinical and pre-clinical vaccine candidates, these efforts have been hindered by factors including HCV antigenic variability and immune evasion. Structure-based and rational vaccine design approaches have capitalized on insights regarding the immune response to HCV and the structures of antibody-bound envelope glycoproteins. Despite successes with other viruses, designing an immunogen based on HCV glycoproteins that can elicit broadly protective immunity against HCV infection is an ongoing challenge. Here, we describe HCV vaccine design approaches where immunogens were selected and optimized through analysis of available structures, identification of conserved epitopes targeted by neutralizing antibodies, or both. Several designs have elicited immune responses against HCV in vivo, revealing correlates of HCV antigen immunogenicity and breadth of induced responses. Recent studies have elucidated the functional, dynamic and immunological features of key regions of the viral envelope glycoproteins, which can inform next-generation immunogen design efforts. These insights and design strategies represent promising pathways to HCV vaccine development, which can be further informed by successful immunogen designs generated for other viruses. MDPI 2021-05-05 /pmc/articles/PMC8148096/ /pubmed/34063143 http://dx.doi.org/10.3390/v13050837 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
Guest, Johnathan D.
Pierce, Brian G.
Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title_full Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title_fullStr Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title_full_unstemmed Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title_short Structure-Based and Rational Design of a Hepatitis C Virus Vaccine
title_sort structure-based and rational design of a hepatitis c virus vaccine
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148096/
https://www.ncbi.nlm.nih.gov/pubmed/34063143
http://dx.doi.org/10.3390/v13050837
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