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

• Published in: Scientific reports Vol. 6; no. 1; p. 30627
• Main Authors: Grzyb, Katarzyna, Czarnota, Anna, Brzozowska, Agnieszka, Cieślik, Anna, Rąbalski, Łukasz, Tyborowska, Jolanta, Bieńkowska-Szewczyk, Krystyna
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.08.2016; Nature Publishing Group
• Subjects: 13; 13/1; 13/109; 631/250/255/234/2513/1551; 631/61/24/590/2294; 64; 64/60; 82/16; 82/80; 82/83; Animals; Antibodies, Neutralizing - blood; Antibody response; Cross Reactions; Cross-reactivity; Epitopes; Gene Expression; Genotypes; Glycoproteins; Hepacivirus - immunology; Hepatitis; Hepatitis C; Hepatitis C Antibodies - blood; Humanities and Social Sciences; Immune response; Immunogenicity; Leishmania - genetics; Mammalian cells; Mice; multidisciplinary; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Science; Vaccines; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral infections; Viral Vaccines - administration & dosage; Viral Vaccines - immunology
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep30627

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.