A novel Schmallenberg virus subunit vaccine candidate protects IFNAR-/- mice against virulent SBV challenge

Hani Boshra,Alejandro Brun,Joseba M Garrido,Sandra Moreno,Nicola G A Abrescia,Isbene Sanchez,Marivi Geijo,Gema Lorenzo,Diego Charro,Gabriel Soares Guerra

doi:10.1038/s41598-020-73424-2

Abstract

Schmallenberg virus (SBV), an arthropod-transmitted pathogenic bunyavirus, continues to be a threat to the European livestock industry, causing morbidity and mortality among young ruminant livestock. Here, we describe a novel SBV subunit vaccine, based on bacterially expressed SBV nucleoprotein (SBV-N) administered with a veterinary-grade Saponin adjuvant. When assayed in an IFNAR-/- mouse model, SBV-N with Saponin induced strong non-neutralizing broadly virus-reactive antibodies, decreased clinical signs, as well as significantly reduced viremia. Vaccination assays also suggest that this level of immune protection is cell mediated, as evidenced by the lack of neutralizing antibodies, as well as interferon-γ secretion observed in vitro. Therefore, based on these results, bacterially expressed SBV-N, co-administered with veterinary-grade Saponin adjuvant may serve as a promising economical alternative to current SBV vaccines, and warrant further evaluation in large ruminant animal models. Moreover, we propose that this strategy may be applicable to other bunyaviruses.

Highlights

Schmallenberg virus (SBV) is an orthobunyavirus of the family Peribunyaviridae, of the newly established order Bunyavirales[1]
While our previous work has detailed vaccine strategies against SBV through DNA vaccination[18], and work by others the recombinant mammalian cell expression of fused viral proteins[19,20], the idea of a simpler and more cost-effective SBV subunit vaccine has yet to be explored. It is with these financial constraints in mind that we propose to generate a more economical SBV vaccine, based on our previous findings that SBV nucleoprotein does have immunoprotective properties based on a potent CD8+-T-cell response
Mice were inoculated with subunit vaccine candidates (SBV N and SBV N + Saponin) and corresponding controls (GFP, GFP + Saponin, Saponin, phosphate-buffered saline (PBS)) at two week intervals

Summary

Introduction

Schmallenberg virus (SBV) is an orthobunyavirus of the family Peribunyaviridae, of the newly established order Bunyavirales[1]. The immune protection conferred to IFNAR-/- mice was not-related with the induction of in vitro neutralizing antibodies Both vaccine targets elicited potent C D8+ T-cell proliferation upon in vitro re-stimulation with inactivated SBV virus, suggesting that the protective immunity conferred to mice using these DNA constructs was primarily cell-mediated. While our previous work has detailed vaccine strategies against SBV through DNA vaccination[18], and work by others the recombinant mammalian cell expression of fused viral proteins[19,20], the idea of a simpler and more cost-effective SBV subunit vaccine has yet to be explored It is with these financial constraints in mind that we propose to generate a more economical SBV vaccine, based on our previous findings that SBV nucleoprotein does have immunoprotective properties based on a potent CD8+-T-cell response. We hypothesized that a recombinant SBV nucleoprotein (SBV-N) can elicit a similar response if administered as a subunit vaccine; and that this response can be further augmented if SBV-N is administered with Saponin, an adjuvant that can stimulate a potent cell-mediated immune response[25]

Methods

Results

Conclusion