BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice

Ebrahim Kord; Farzin Roohvand; Jean Dubuisson; Thibaut Vausselin; Hosein Nasr Azadani; Abolfazl Keshavarz; Ahmad Nejati; Katayoun Samimi-Rad

doi:10.1186/s13027-021-00407-x

BacMam virus-based surface display for HCV E2 glycoprotein induces strong cross-neutralizing antibodies and cellular immune responses in vaccinated mice

Infect Agent Cancer. 2021 Dec 18;16(1):69. doi: 10.1186/s13027-021-00407-x.

Authors

Ebrahim Kord^{1

2}, Farzin Roohvand³, Jean Dubuisson⁴, Thibaut Vausselin⁴, Hosein Nasr Azadani¹, Abolfazl Keshavarz¹, Ahmad Nejati¹, Katayoun Samimi-Rad⁵

Affiliations

¹ Department of Virology, School of Public Health, Tehran University of Medical Sciences, Enqelab Square, P.O. Box 1417613151, Tehran, Iran.
² Infectious Diseases and Tropical Medicine Research Center, Resistant Tuberculosis Institute, Zahedan University of Medical Sciences, Zahedan, Iran.
³ Department of Virology, Pasteur Institute of Iran (IPI), No. 69, Pasteur Ave, P.O. Box 1316943551, Tehran, Iran.
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, 59021, Lille Cedex, France.
⁵ Department of Virology, School of Public Health, Tehran University of Medical Sciences, Enqelab Square, P.O. Box 1417613151, Tehran, Iran. ksamimirad@sina.tums.ac.ir.

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.

Keywords: BacMam virus; Baculovirus; HCV; Surface display; Vaccine; gpE2.