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A Dna Vaccine Expressing Fusion Protein E2-Nt(Gp96) Induces Hepatitis C Virus Cross-Neutralizing Antibody in Balb/C Mice Publisher



Kord E1 ; Dubuisson J2 ; Vausselin T2 ; Amirzargar AA3, 4 ; Yekaninejad MS5 ; Hajikhezri Z1 ; Keshavarz A1 ; Samimirad K1
Authors
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Authors Affiliations
  1. 1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL- Center for Infection and Immunity of Lille, Lille, F-59000, France
  3. 3. Molecular Immunology Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Immunogenetic Laboratory, Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Department of Epidemiology and Biostatistics, School of public Health, Tehran University of Medical Sciences, Tehran, Iran

Source: Hepatitis Monthly Published:2019


Abstract

Background: Development of an effective prophylactic vaccine is the optimal long-term goal for the eventual control of HCV infection. An effective HCV vaccine should be able to elicit neutralizing antibodies (NAbs). Glycoprotein E2 of HCV is the major target for NAbs. Methods: In this study, we designed and constructed a DNA vaccine (pcDNA-E2-NT(gp96)) encoding a fusion protein composed of HCV E2 ectodomain (genotype 1a) and N-terminal domain of gp96 as a biological adjuvant. Two possible forms of a fusion protein, namely E2-NT(gp96) and NT(gp96)-E2, were made and subjected to in silico modeling and analysis. After the selection of the best form and confirmation its expression capacity in COS-7 cells, recombinant pcDNA-E2-NT(gp96) plasmid was generated by cloning of target genes into pcDNA3.1(+) plasmid. Constructed DNA vaccine immunogenicity was evaluated in BALB/c mice by measurement specific antibodies by ELISA and their neutralization capacity by neutralization assay. Results: In silico modeling and analysis showed that the E2-NT(gp96) structure was more valid than NT(gp96)-E2. Docking result revealed that the selected fusion protein had a high tendency for interaction with the main receptor (CD81) of HCV. GFP expression in COS-7 cells confirmed the E2-NT(gp96) expression capacity. Restriction enzyme digestion and sequencing results confirmed the integrity of the constructed plasmid. ELISA results showed that the pcDNA-E2-NT(gp96) induced high titers of specific antibodies in immunized mice. The sera of immunized mice cross-neutralized JFH1/HCVcc genotype 2a by 55% relative to pre-immune sera. Conclusions: Total results showed that the generated DNA vaccine induced potent immune responses in immunized mice. Therefore, our findings are sufficiently encouraging to propose the pcDNA-E2-NT(gp96) as a promising vaccine candidate for HCV infection. © 2019, Author(s).
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