A single vaccination with four-segmented rift valley fever virus prevents vertical transmission of the wild-type virus in pregnant ewes

Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus that causes severe outbreaks among wild and domesticated ruminants, of which sheep are the most susceptible. Outbreaks are characterised by high mortality rates among new-born lambs and abortion storms, in which all pregnant ewes in a flock may abort their foetuses. In endemic areas, Rift Valley fever (RVF) can be controlled by vaccination with either inactivated or live-attenuated vaccines. Inactivated vaccines are safe for animals during all physiological stages, including pregnancy. However, optimal efficacy of these vaccines depends on multiple vaccinations and yearly re-vaccination. Live-attenuated vaccines are generally highly efficacious after a single vaccination, but currently available live-attenuated vaccines may transmit to the ovine foetus, resulting in stillbirths, congenital malformations or abortion. We have previously reported the development of a novel live-attenuated RVFV vaccine, named RVFV-4s. This vaccine virus was created by splitting the M genome segment and deleting the major virulence determinant NSs, and was shown to be safe even for the most susceptible species, including pregnant ewes. The demonstrated efficacy and safety profile suggests that RVFV-4s holds promise for veterinary and human application. The RVFV-4s vaccine for veterinary application, here referred to as vRVFV-4s, was shown to provide complete protection after a single vaccination of lambs, goats and cattle. In this work, we evaluated the efficacy of the vRVFV-4s vaccine in pregnant ewes. Anticipating on the extremely high susceptibility of pregnant ewes for RVFV, both a single vaccination and double vaccination were evaluated in two independent experiments. The combined results suggest that a single vaccination with vRVFV-4s is sufficient to protect pregnant ewes and to prevent transmission to the ovine foetus.