Paul Wichgers Schreur (Wageningen Bioveterinary Research)

Summary of presentation:
Rift Valley fever virus (RVFV) is a mosquito‑borne zoonotic bunyavirus responsible for severe, recurrent outbreaks across Africa and the Arabian Peninsula, most recently illustrated by a major outbreak in humans and animals in Senegal. Human infection occurs through bites from infected mosquitoes or contact with body fluids or tissues of infected animals. While most cases present as a self‑limiting febrile illness, a minority progress to severe disease, with an overall case‑fatality rate of approximately 1–2%. No licensed vaccines for human use are currently available. Because RVFV can cause large epidemics and lacks effective countermeasures, it is included on the WHO Blueprint list. With support from CEPI, several vaccine candidates have advanced beyond the R&D phase. One of these, a four‑segmented RVFV live-attenuated vaccine candidate (hRVFV‑4s), is being developed for human use by a consortium of five partners. Preclinical studies across multiple animal models have shown that a single dose of hRVFV‑4s provides complete protection without safety concerns. A first‑in‑human Phase I clinical trial in healthy volunteers in Belgium subsequently showed no significant safety issues in any dose group and confirmed absence of vaccine virus shedding in urine, saliva and semen. The vaccine elicited robust anti‑nucleocapsid antibody and T‑cell responses across all doses, along with a strong, dose‑dependent neutralizing antibody response. These antibodies were further shown to confer protection in animal models following passive transfer. Together, these findings indicate that the hRVFV‑4s vaccine holds strong promise for preventing the burden of Rift Valley fever.