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Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex

Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are the main inducers of a cross-neutralizing antibody response which plays an important role in the early phase of viral infection. Correctly folded and immunologically active E1E2 complex can be expressed in mammalian cells, though the produ...

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Autores principales: Grzyb, Katarzyna, Czarnota, Anna, Brzozowska, Agnieszka, Cieślik, Anna, Rąbalski, Łukasz, Tyborowska, Jolanta, Bieńkowska-Szewczyk, Krystyna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969751/
https://www.ncbi.nlm.nih.gov/pubmed/27481352
http://dx.doi.org/10.1038/srep30627
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author Grzyb, Katarzyna
Czarnota, Anna
Brzozowska, Agnieszka
Cieślik, Anna
Rąbalski, Łukasz
Tyborowska, Jolanta
Bieńkowska-Szewczyk, Krystyna
author_facet Grzyb, Katarzyna
Czarnota, Anna
Brzozowska, Agnieszka
Cieślik, Anna
Rąbalski, Łukasz
Tyborowska, Jolanta
Bieńkowska-Szewczyk, Krystyna
author_sort Grzyb, Katarzyna
collection PubMed
description Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are the main inducers of a cross-neutralizing antibody response which plays an important role in the early phase of viral infection. Correctly folded and immunologically active E1E2 complex can be expressed in mammalian cells, though the production process might still prove restrictive, even if the immunological response of a vaccine candidate is positive. Here, we report a characterization and immunogenicity study of a full-length (fE1E2) and soluble version of the E1E2 complex (tE1E2) from genotype 1a, successfully expressed in the cells of Leishmania tarentolae. In a functional study, we confirmed the binding of both Leishmania-derived E1E2 complexes to the CD-81 receptor and the presence of the major epitopes participating in a neutralizing antibody response. Both complexes were proved to be highly immunogenic in mice and elicited neutralizing antibody response. Moreover, cross-reactivity of the mouse sera was detected for all tested HCV genotypes with the highest signal intensity observed for genotypes 1a, 1b, 5 and 6. Since the development of a prophylactic vaccine against HCV is still needed to control the global infection, our Leishmania-derived E1E2 glycoproteins could be considered a potential cost-effective vaccine candidate.
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spelling pubmed-49697512016-08-11 Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex Grzyb, Katarzyna Czarnota, Anna Brzozowska, Agnieszka Cieślik, Anna Rąbalski, Łukasz Tyborowska, Jolanta Bieńkowska-Szewczyk, Krystyna Sci Rep Article Hepatitis C virus (HCV) envelope glycoproteins E1 and E2 are the main inducers of a cross-neutralizing antibody response which plays an important role in the early phase of viral infection. Correctly folded and immunologically active E1E2 complex can be expressed in mammalian cells, though the production process might still prove restrictive, even if the immunological response of a vaccine candidate is positive. Here, we report a characterization and immunogenicity study of a full-length (fE1E2) and soluble version of the E1E2 complex (tE1E2) from genotype 1a, successfully expressed in the cells of Leishmania tarentolae. In a functional study, we confirmed the binding of both Leishmania-derived E1E2 complexes to the CD-81 receptor and the presence of the major epitopes participating in a neutralizing antibody response. Both complexes were proved to be highly immunogenic in mice and elicited neutralizing antibody response. Moreover, cross-reactivity of the mouse sera was detected for all tested HCV genotypes with the highest signal intensity observed for genotypes 1a, 1b, 5 and 6. Since the development of a prophylactic vaccine against HCV is still needed to control the global infection, our Leishmania-derived E1E2 glycoproteins could be considered a potential cost-effective vaccine candidate. Nature Publishing Group 2016-08-02 /pmc/articles/PMC4969751/ /pubmed/27481352 http://dx.doi.org/10.1038/srep30627 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Grzyb, Katarzyna
Czarnota, Anna
Brzozowska, Agnieszka
Cieślik, Anna
Rąbalski, Łukasz
Tyborowska, Jolanta
Bieńkowska-Szewczyk, Krystyna
Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title_full Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title_fullStr Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title_full_unstemmed Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title_short Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex
title_sort immunogenicity and functional characterization of leishmania-derived hepatitis c virus envelope glycoprotein complex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4969751/
https://www.ncbi.nlm.nih.gov/pubmed/27481352
http://dx.doi.org/10.1038/srep30627
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