Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination

P.J. Wichgers Schreur, H.C.M. Kant-Eenbergen, L.J.M. van Keulen, R.J.M. Moormann, J.A. Kortekaas

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9 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1459-1464
JournalVaccine
Volume33
Issue number12
DOIs
Publication statusPublished - 17 Mar 2015

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Rift Valley fever virus
Immunity
Sheep
Vaccination
immunity
vaccination
sheep
viruses
lambs
Genome
Viruses
Bunyaviridae
Virus Assembly
Virus Internalization
Protein Precursors
genome
Viremia
viremia
Ruminants
dosage

Cite this

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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.",
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Four-segmented Rift Valley fever virus induces sterile immunity in sheep after a single vaccination. / Wichgers Schreur, P.J.; Kant-Eenbergen, H.C.M.; van Keulen, L.J.M.; Moormann, R.J.M.; Kortekaas, J.A.

In: Vaccine, Vol. 33, No. 12, 17.03.2015, p. 1459-1464.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Wichgers Schreur, P.J.

AU - Kant-Eenbergen, H.C.M.

AU - van Keulen, L.J.M.

AU - Moormann, R.J.M.

AU - Kortekaas, J.A.

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DO - 10.1016/j.vaccine.2015.01.077

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SN - 0264-410X

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