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In our study, novel subunit vaccines on the basis of an amino-terminal domain of SBV Gc of 234 amino acids (\u201cGc Amino\u201d) first were tested and selected using a lethal small animal challenge model and then the best performing formulations also were tested in cattle. We could show that neither E. coli expressed nor the reduced form of \u201cGc Amino\u201d protected from SBV infection. In contrast, both, immunization with \u201cGc Amino\u201d-encoding DNA plasmids and \u201cGc-amino\u201d expressed in a mammalian system, conferred protection in up to 66% of the animals. Interestingly, the best performance was achieved with a multivalent antigen containing the covalently linked Gc domains of both, SBV and the related Akabane virus. All vaccinated cattle and mice were fully protected against SBV challenge infection. Furthermore, in the absence of antibodies against the viral N-protein, differentiation between vaccinated and field-infected animals allows an SBV marker vaccination concept. Moreover, the presented vaccine design also could be tested for other members of the Simbu serogroup and might allow the inclusion of additional immunogenic domains.<\/jats:p>","DOI":"10.1038\/srep42500","type":"journal-article","created":{"date-parts":[[2017,2,13]],"date-time":"2017-02-13T10:18:03Z","timestamp":1486981083000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["The N-terminal domain of Schmallenberg virus envelope protein Gc is highly immunogenic and can provide protection from infection"],"prefix":"10.1038","volume":"7","author":[{"given":"Kerstin","family":"Wernike","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Aebischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gleyder","family":"Roman-Sosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Beer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,2,13]]},"reference":[{"key":"BFsrep42500_CR1","doi-asserted-by":"crossref","unstructured":"Calisher, C. 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