In Vitro and In Vivo Attenuation of Vesicular Stomatitis Virus (VSV) by Phosphoprotein Deletion

Abstract

Vesicular stomatitis virus (VSV) is highly immunogenic and able to stimulate both innate and adaptive immune responses. However, its ability to induce adverse effects has held back the use of VSV as a potential vaccine vector. In this study we developed VSV-ΔP, a safe yet potent replication-defective recombinant VSV in which the phosphoprotein (P) gene was deleted. VSV-ΔP replicated only in supporting cells expressing P (BHK-P cells) and at levels more than 2 logs lower than VSV. In vivo studies indicated that the moderate replication of VSV-ΔP in vitro was associated with the attenuation of this virus in the mouse model, whereas mice intracranially injected with VSV succumbed to neurotoxicity. Furthermore, we constructed VSV and VSV-ΔP expressing a variety of antigens including hemagglutinin-neuraminidase (HN) from Newcastle disease virus (NDV), hemagglutinin (HA) from either a 2009 H1N1 pandemic influenza virus (pdm/09) or the avian H7N9. VSV and VSV-ΔP incorporated the foreign antigens on their surface resulting in induction of robust neutralizing antibody, serum IgG, and hemagglutination inhibition (HAI) titers against their corresponding viruses. These results indicated that VSV with P gene deletion was attenuated in vitro and in vivo, and possibly expressed the foreign antigen on its surface. Therefore, the P gene-deletion strategy may offer a potentially useful and safer approach for attenuating negative-sense RNA viruses which use phosphoprotein as a cofactor for viral replication.

GSH-ZnS Nanoparticles Exhibit High-Efficiency and Broad-Spectrum Antiviral Activities via Multistep Inhibition Mechanisms

“…PRV is a herpesvirus that mainly causes viral diseases characterized by nervous system disorders, respiratory disorders, and reproductive failure in pigs of different ages, including newborn piglets, growing-finishing pigs, and sows . VSV is a rhabdovirus that causes vesicular lesions around the teats, mouth, and hoofs of cattle, horses, and swine during natural infection, which is also reported as a potential pathogen for humans . Currently, PEDV, PRV, and VSV have caused huge economic losses to the livestock industry.…”

PEDV ORF3 Independently Regulates IκB Kinase β-Mediated NF-κB and IFN-β Promoter Activities

“…PEDV AV12 _ORF3 [12] was propagated in VeroE6 cells in Opti-MEM ® containing recombinant trypsin (2 µg/mL) (Thermo Scientific, Waltham, MA, USA). The recombinant vesicular stomatitis virus (VSV) expressing the mCherry protein (VSV-mCherry) constructed in our laboratory was previously described [29].…”

Antibody Immunity Induced by H7N9 Avian Influenza Vaccines: Evaluation Criteria, Affecting Factors, and Implications for Rational Vaccine Design

“…However, the safety of H7N9 LAIVs must be evaluated sufficiently because the two surface proteins are derived from fatal H7N9 isolates. Moreover, viral-vectored H7N9 vaccines based on modified vaccinia virus, vesicular stomatitis virus, and human adenovirus were also immunogenic and efficacious in animal models (Kreijtz et al, 2015 ; Cao et al, 2016a ; Wongthida et al, 2016 ). However, an H7HA-expressing vaccine based on parainfluenza virus 5 can provide full protection against H7N9 infection in mice, whereas it failed to induce any measurable antibody titers, suggesting a potential role of cellular immunity in protection (Chia et al, 2015 ).…”