Assessment of BoHV-4-based vector vaccine intranasally administered in a hamster challenge model of lung disease

Seok-Chan Park; Laura Conti; Valentina Franceschi; Byungkwan Oh; Myeon-Sik Yang; Gaeul Ham; Antonino Di Lorenzo; Elisabetta Bolli; Federica Cavallo; Bumseok Kim; Gaetano Donofrio

doi:10.3389/fimmu.2023.1197649

Assessment of BoHV-4-based vector vaccine intranasally administered in a hamster challenge model of lung disease

Front Immunol. 2023 Jul 6:14:1197649. doi: 10.3389/fimmu.2023.1197649. eCollection 2023.

Affiliations

¹ Biosafety Research Institute and Laboratory of Veterinary Pathology, College of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of Korea.
² Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
³ Department of Medical Veterinary Sciences, University of Parma, Parma, Italy.

Abstract

Introduction: Bovine herpesvirus 4 (BoHV-4) is a bovine Rhadinovirus not associated with a specific pathological lesion or disease and experimentally employed as a viral vector vaccine. BoHV-4-based vector (BoHV-4-BV) has been shown to be effective in immunizing and protecting several animal species when systemically administrated through intramuscular, subcutaneous, intravenous, or intraperitoneal routes. However, whether BoHV-4-BV affords respiratory disease protection when administered intranasally has never been tested.

Methods: In the present study, recombinant BoHV-4, BoHV-4-A-S-ΔRS-HA-ΔTK, was constructed to deliver an expression cassette for the SARS-CoV-2 spike glycoprotein, and its immunogenicity, as well as its capability to transduce cells of the respiratory tract, were tested in mice. The well-established COVID-19/Syrian hamster model was adopted to test the efficacy of intranasally administered BoHV-4-A-S-ΔRS-HA-ΔTK in protecting against a SARS-CoV-2 challenge.

Results: The intranasal administration of BoHV-4-A-S-ΔRS-HA-ΔTK elicited protection against SARS-CoV-2, with improved clinical signs, including significant reductions in body weight loss, significant reductions in viral load in the trachea and lungs, and significant reductions in histopathologic lung lesions compared to BoHV-4-A-S-ΔRS-HA-ΔTK administered intramuscularly.

Discussion: These results suggested that intranasal immunization with BoHV-4-BV induced protective immunity and that BoHV-4-BV could be a potential vaccine platform for the protection of other animal species against respiratory diseases.

Keywords: BoHV-4-based vector; immune response; intranasal vaccination; lung disease; vaccine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intranasal
Animals
COVID-19* / prevention & control
Cricetinae
Herpesvirus 4, Bovine*
Mice
SARS-CoV-2
Viral Vaccines*

Substances

Viral Vaccines

Grants and funding

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2019R1A6A1A03033084), and internal funding from Parma University.