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

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.

The Adaptive Immune Response against Bunyaviruses

“…Similar findings were observed for SBV vaccination, where DNA encoding the Gc ectodomain induced CD8+ T cell-mediated protection [34]. Additionally, subunitor DNA-based N vaccines have both been shown to reduce clinical signs and significantly decrease viremia upon SBV challenge, eliciting CD8+ T cell-mediated responses [34,36].…”

Antibodies Targeting the CCHFV Nucleocapsid Protein Require TRIM21 for Protection

“…Together, these data and our findings suggest that NPspecific antibody may be a key protective immune response during acute infections. Intriguingly, NPbased vaccines have demonstrated efficacy for other bunyaviruses such as Lassa virus [39], Rift Valley Fever Virus [40][41][42][43], Schmallenberg Virus [44] and Hantaviruses [45][46][47] demonstrating immunity against the bunyaviral NP is a broadly protective mechanism. However, in these studies the role of NP-specific antibody in protection was not investigated.…”

The Adaptive Immune Response against Bunyavirales

“…Similar findings were observed for SBV vaccination, where DNA encoding the Gc ectodomain induced CD8+ T cell-mediated protection [ 34 ]. Additionally, subunit- or DNA-based N vaccines have both been shown to reduce clinical signs and significantly decrease viremia upon SBV challenge, eliciting CD8+ T cell-mediated responses [ 34 , 36 ].…”