title: Comparative efficacy of two next-generation Rift Valley fever vaccines.
abstract: Rift Valley fever virus (RVFV) is a re-emerging zoonotic bunyavirus of the genus Phlebovirus. A natural isolate containing a large attenuating deletion in the small (S) genome segment previously yielded a highly effective vaccine virus, named Clone 13. The deletion in the S segment abrogates expression of the NSs protein, which is the major virulence factor of the virus. To develop a vaccine of even higher safety, a virus named R566 was created by natural laboratory reassortment. The R566 virus combines the S segment of the Clone 13 virus with additional attenuating mutations on the other two genome segments M and L, derived from the previously created MP-12 vaccine virus. To achieve the same objective, a nonspreading RVFV (NSR-Gn) was created by reverse-genetics, which not only lacks the NSs gene but also the complete M genome segment. We have now compared the vaccine efficacies of these two next-generation vaccines and included the Clone 13 vaccine as a control for optimal efficacy. Groups of eight lambs were vaccinated once and challenged three weeks later. All mock-vaccinated lambs developed high fever and viremia and three lambs did not survive the infection. As expected, lambs vaccinated with Clone 13 were protected from viremia and clinical signs. Two lambs vaccinated with R566 developed mild fever after challenge infection, which was associated with low levels of viral RNA in the blood, whereas vaccination with the NSR-Gn vaccine completely prevented viremia and clinical signs.
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre (CVI-WUR), P. O. Box 65, 8200 AB Lelystad, The Netherlands. Electronic address: jeroen.kortekaas@wur.nl.
authors: J
authors: J
authors: Kortekaas
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre (CVI-WUR), P. O. Box 65, 8200 AB Lelystad, The Netherlands; Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands.
authors: N
authors: N
authors: Oreshkova
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre (CVI-WUR), P. O. Box 65, 8200 AB Lelystad, The Netherlands.
authors: L
authors: L
authors: van Keulen
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre (CVI-WUR), P. O. Box 65, 8200 AB Lelystad, The Netherlands.
authors: J
authors: J
authors: Kant
authors: Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands.
authors: B J
authors: BJ
authors: Bosch
authors: Institut Pasteur, Unité de Génétique Moléculaire des Bunyavirus, 75724 Paris Cedex 15, France.
authors: M
authors: M
authors: Bouloy
authors: Intervet International BV/Merck Sharp and Dohme (MSD) Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands.
authors: V
authors: V
authors: Moulin
authors: Intervet International BV/Merck Sharp and Dohme (MSD) Animal Health, Wim de Körverstraat 35, 5831 AN Boxmeer, The Netherlands. Electronic address: DannyGoovaerts@skynet.be.
authors: D
authors: D
authors: Goovaerts
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre (CVI-WUR), P. O. Box 65, 8200 AB Lelystad, The Netherlands; Department of Infectious Diseases and Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584 CL, Utrecht, The Netherlands.
authors: R J M
authors: RJ
authors: Moormann
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D009500:Neutralization Tests; D012367:RNA, Viral / Q000097:blood; D011897:Random Allocation; D016865:Reassortant Viruses / Q000276:immunology; D012295:Rift Valley Fever / Q000517:prevention & control*; D012296:Rift Valley fever virus / Q000276:immunology; D012756:Sheep / Q000276:immunology; D012757:Sheep Diseases / Q000517:prevention & control* / Q000821:virology; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D014766:Viremia
chemical_list: D000914:Antibodies, Viral; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Clone 13; Comparative; NSR-Gn; Nonspreading; R566; Replicon; Rift Valley fever virus; Sheep; Vaccine