title: Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination.
abstract: Rift Valley fever virus (RVFV), a mosquito-borne virus in the Bunyaviridae family, causes recurrent outbreaks with severe disease in ruminants and occasionally humans. The virus comprises a segmented genome consisting of a small (S), medium (M) and large (L) RNA segment of negative polarity. The M-segment encodes a glycoprotein precursor (GPC) protein that is co-translationally cleaved into Gn and Gc, which are required for virus entry and fusion. Recently we developed a four-segmented RVFV (RVFV-4s) by splitting the M-genome segment, and used this virus to study RVFV genome packaging. Here we evaluated the potential of a RVFV-4s variant lacking the NSs gene (4s-ΔNSs) to induce protective immunity in sheep. Groups of seven lambs were either mock-vaccinated or vaccinated with 10(5) or 10(6) tissue culture infective dose (TCID50) of 4s-ΔNSs via the intramuscular (IM) or subcutaneous (SC) route. Three weeks post-vaccination all lambs were challenged with wild-type RVFV. Mock-vaccinated lambs developed high fever and high viremia within 2 days post-challenge and three animals eventually succumbed to the infection. In contrast, none of the 4s-ΔNSs vaccinated animals developed clinical signs during the course of the experiment. Vaccination with 10(5) TCID50 via the IM route provided sterile immunity, whereas a 10(6) dose was required to induce sterile immunity via SC vaccination. Protection was strongly correlated with the presence of RVFV neutralizing antibodies. This study shows that 4s-ΔNSs is able to induce sterile immunity in the natural target species after a single vaccination, preferably administrated via the IM route.
authors: Department of Virology, Central Veterinary Institute, Part of Wageningen University and Research Centre, Lelystad, The Netherlands. Electronic address: paul.wichgersschreur@wur.nl.
authors: Paul J
authors: PJ
authors: Wichgers Schreur
authors: Department of Virology, Central Veterinary Institute, Part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors: Jet
authors: J
authors: Kant
authors: Department of Virology, Central Veterinary Institute, Part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors: Lucien
authors: L
authors: van Keulen
authors: Department of Virology, Central Veterinary Institute, Part of Wageningen University and Research Centre, Lelystad, The Netherlands; Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors: Rob J M
authors: RJ
authors: Moormann
authors: Department of Virology, Central Veterinary Institute, Part of Wageningen University and Research Centre, Lelystad, The Netherlands.
authors: Jeroen
authors: J
authors: Kortekaas
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood* / Q000276:immunology; D007110:Immunity, Active; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D009154:Mutation; D012295:Rift Valley Fever / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000235:genetics / Q000276:immunology*; D012756:Sheep; D012757:Sheep Diseases / Q000517:prevention & control* / Q000821:virology; D034561:Sheep, Domestic / Q000276:immunology* / Q000821:virology; D014611:Vaccination / Q000662:veterinary; D014613:Vaccines, Attenuated; D014765:Viral Vaccines / Q000276:immunology; D014766:Viremia / Q000662:veterinary / Q000821:virology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Challenge; Four-segmented; Rift Valley fever virus; Sheep; Vaccination