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Bacmam Virus-Based Surface Display for Hcv E2 Glycoprotein Induces Strong Cross-Neutralizing Antibodies and Cellular Immune Responses in Vaccinated Mice Publisher



Kord E1, 2 ; Roohvand F3 ; Dubuisson J4 ; Vausselin T4 ; Nasr Azadani H1 ; Keshavarz A1 ; Nejati A1 ; Samimirad K1
Authors
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Authors Affiliations
  1. 1. Department of Virology, School of Public Health, Tehran University of Medical Sciences, Enqelab Square, P.O. Box 1417613151, Tehran, Iran
  2. 2. Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran
  3. 3. Department of Virology, Pasteur Institute of Iran (IPI), No. 69, Pasteur Ave, P.O. Box 1316943551, Tehran, Iran
  4. 4. CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, Batiment, IBL, CS50477, Molecular & Cellular Virology, U1019 - UMR 8204 - CIIL- Center for Infection and Immunity of Lille, University Lille, Lille Cedex, 59021, France

Source: Infectious Agents and Cancer Published:2021


Abstract

Background: Despite recent advancements, limitations in the treatment and control of hepatitis C virus (HCV) infection reprioritized the studies for invention of an efficient HCV vaccine to elicit strong neutralizing antibodies (NAbs) and cellular responses. Methods: Herein, we report molecular construction of a BacMam virus-based surface display for a subtype-1a HCV gpE2 (Bac-CMV-E2-gp64; Bac) that both expressed and displayed gpE2 in mammalian cells and bacouloviral envelope, respectively. Results: Assessments by western blotting, Immunofluorescence and Immunogold-electron microscopy indicated the proper expression and incorporation in insect cell and baculovirus envelope, respectively. Mice immunized in three different prime-boost immunization groups of: Bac/Bac, Bac/Pro (bacoulovirus-derived gpE2) and Bac/DNA (plasmid DNA (pCDNA)-encoding gpE2) developed high levels of IgG and IFN-γ (highest for Bac/Bac group) indicating the induction of both humeral and cellular immune responses. Calculation of the IgG2a/IgG1 and IFN-γ/IL-4 ratios indicated a Th1 polarization of immune responses in the Bac/Bac and Bac/DNA groups but a balanced Th1-Th2 phenotype in the Bac/Pro group. Sera of the mice in the Bac/Bac group provided the highest percentage of cross-NAbs against a subtype-2a HCVcc (JFH1) compared to Bac/Pro and Bac/DNA groups (62% versus 41% and 6%). Conclusions: Results indicated that BacMam virus-based surface display for gpE2 might act as both subunit and DNA vaccine and offers a promising strategy for development of HCV vaccine for concurrent induction of strong humoral and cellular immune responses. © 2021, The Author(s).
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