Immunization with a small fragment of the Schmallenberg virus nucleoprotein highly conserved across the Orthobunyaviruses of the Simbu serogroup reduces viremia in SBV challenged IFNAR-/- mice

• Published in: Vaccine Vol. 41; no. 20; pp. 3275 - 3284
• Main Authors: Guerra, Gabriel Soares, Barriales, Diego, Lorenzo, Gema, Moreno, Sandra, Anguita, Juan, Brun, Alejandro, Abrescia, Nicola G.A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 11.05.2023; Elsevier Limited
• Subjects: Animals; Bunyaviridae Infections - prevention & control; Bunyaviridae Infections - veterinary; Cattle; Cattle Diseases - prevention & control; Cell-mediate immunity; Cloning; Crystal structure; Diarrhea; Domains; E coli; Fetuses; Genomes; Homology; Humans; Immunization; Infections; Ions; Mice; Milk production; Morbidity; Nanoparticles; Nucleoproteins; Nucleoproteins - genetics; Orthobunyavirus; Orthobunyavirus - genetics; Pan-vaccine; Pathogens; Polypeptides; Protein expression; Proteins; Ruminants; Schmallenberg virus; Serogroup; Splenocytes; Subunit vaccine; Vaccines; Viremia; Viremia - prevention & control; Viruses; Weight loss; γ-Interferon; United Kingdom > UK; Belgium; United States > US; Germany; Orthobunyavirus; Pan-vaccine; Cell-mediate immunity; Subunit vaccine; Schmallenberg virus
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2023.04.027

•A short fragment of the nucleoprotein of Schmallenberg virus has been identified as candidate subunit vaccine.•The candidate subunit vaccine reduces viraemia in infected mice.•The subunit vaccine shares high sequence homology with the nucleoproteins of the members of the Simbu serogroup. Schmallenberg Virus (SBV), an arbovirus from the Peribunyaviridae family and Orthobunyavirus genus, was discovered in late 2011 in Germany and has been circulating in Europe, Asia and Africa ever since. The virus causes a disease associated with ruminants that includes fever, fetal malformation, drop in milk production, diarrhoea and stillbirths, becoming a burden for small and large farms. Building on previous studies on SBV nucleoprotein (SBV-N) as a promising vaccine candidate, we have investigated the possible protein regions responsible for protection. Based on selective truncation of domains designed from the available crystal structure of the SBV-N, we identified both the N-terminal domain (N-term; Met1 – Thr133) and a smaller fragment within (C4; Met1 – Ala58) as vaccine prototypes. Two injections of the N-term and C4 polypeptides protected mice knockout for type I interferon (IFN) receptors (IFNAR-/-) challenged with virulent SBV, opposite to control groups that presented severe signs of morbidity and weight loss. Viremia analyses along with the presence of IFN-γ secreted from splenocytes re-stimulated with the N-terminal region of the protein corroborate that these two portions of SBV-N can be employed as subunit vaccines. Apart from both proteinaceous fragments being easily produced in bacterial cells, the C4 polypeptide shares a high sequence homology (∼87.1 %) with the corresponding region of nucleoproteins of several viruses of the Simbu serogroup, a group of Orthobunyaviruses that comprises SBV and veterinary pathogens like Akabane virus and human infecting viruses like Oropouche. Thus, we propose that this smaller fragment is better suited for vaccine nanoparticle formulation, and it paves the way to further research with other related Orthobunyaviruses.