Vaccine and strucutural studies of schamallenberg virus

Abstract

Schmallenberg Virus (SBV) is an arbovirus that belongs to the Peribunyaviridae family and Orthobunyavirus genus, being its closely counterparts Bunyamwera virus (BUNV) and Akabane Virus. SBV was discovered in late 2011 in Germany, it is transmitted by midges¿ bite and have been spreading on Europe, Asia and Africa ever since. The virus causes a disease associated with ruminants that includes fever, drop on milk production, diarrhoea and stillbirths, becoming a burden for small and large farms since its discovery. The SBV virion is pleomorphic and enveloped, enclosing its ribonucleoproteins, formed by the Nucleoprotein (SBV-N) in association with the segmented negative-sense RNA genome, beneath the lipid bilayer. The viral membrane is decorated by the GC and GN glycoproteins that together form the viral spike, the main mediators of viral infection. Among Orthobunyaviruses, the BUNV glycoprotein spike was already structurally described by cryoEM. On the other hand, structural data on SBV for its glycoprotein spikes and the whole virons and are currently very scarce. Concomitantly, due to the increasing spread of the arthropod vectors, there is a growing demand for alternative vaccines formulations against SBV. Hopefully, new prototypes will enter into the market in the future, complementing the current costly unattractive inactivated vaccines against SBV. The present work builds on previous studies from our findings on SBV-N as a promising vaccine candidate. We have investigatedwhich regions from SBV-N are responsible for protection. Based on state-of-art immunological assays using mice models, we have identified both the N-terminal domain (N-term; Met1-Thr133) and a smaller fragment of it (C4; Met1-Ala58) as promising subunit vaccine prototypes. For the structural characterization of SBV, we have optimized purification protocols in order to obtain viral particles for different EM methodologies. This allowed preliminary analyses of the whole virion morphology and the glycoprotein spikes. Complementing vaccinology and structural studies, the present work proposes new immunogens against SBV infection at the same time that it enriches the current knowledge on the SBV morphology. Altogether, these findings are pivotal for a better understanding of the SBV pathology, finally allowing to tackle more efficiently this important veterinary pathogen in the inevitable outbreaks to come.