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.