Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10964706 | Vaccine | 2015 | 6 Pages |
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-ÎNSs) to induce protective immunity in sheep. Groups of seven lambs were either mock-vaccinated or vaccinated with 105 or 106 tissue culture infective dose (TCID50) of 4s-ÎNSs 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-ÎNSs vaccinated animals developed clinical signs during the course of the experiment. Vaccination with 105 TCID50 via the IM route provided sterile immunity, whereas a 106 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-ÎNSs is able to induce sterile immunity in the natural target species after a single vaccination, preferably administrated via the IM route.
Keywords
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Immunology
Authors
Paul J. Wichgers Schreur, Jet Kant, Lucien van Keulen, Rob J.M. Moormann, Jeroen Kortekaas,