title: Immunogenicity and functional characterization of Leishmania-derived hepatitis C virus envelope glycoprotein complex.
abstract: 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.
authors.affiliation: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grzyb
authors.affiliation: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Czarnota
authors.affiliation: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Brzozowska
authors.affiliation: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Cieślik
authors.affiliation: Laboratory of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Rąbalski
authors.affiliation: Laboratory of Recombinant Vaccines, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Tyborowska
authors.affiliation: Laboratory of Virus Molecular Biology, Intercollegiate Faculty of Biotechnology of the University of Gdańsk and Medical University of Gdańsk, Gdańsk, 80-307, Poland.
authors.forename: Krystyna
authors.initials: K
authors.lastname: Bieńkowska-Szewczyk
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D003429:Cross Reactions; D015870:Gene Expression; D016174:Hepacivirus / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000097:blood; D007891:Leishmania / Q000235:genetics; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C091015:glycoprotein E2, Hepatitis C virus