Perspectives of Next-Generation Live-Attenuated Rift Valley Fever Vaccines for Animal and Human Use

Live-attenuated Rift Valley fever (RVF) vaccines transiently replicate in the vaccinated host, thereby effectively initiating an innate and adaptive immune response. Rift Valley fever virus (RVFV)-specific neutralizing antibodies are considered the main correlate of protection. Vaccination with classical live-attenuated RVF vaccines during gestation in livestock has been associated with fetal malformations, stillbirths, and fetal demise. Facilitated by an increased understanding of the RVFV infection and replication cycle and availability of reverse genetics systems, novel rationally-designed live-attenuated candidate RVF vaccines with improved safety profiles have been developed. Several of these experimental vaccines are currently advancing beyond the proof-of-concept phase and are being evaluated for application in both animals and humans. We here provide perspectives on some of these next-generation live-attenuated RVF vaccines and highlight the opportunities and challenges of these approaches to improve global health.

Automated summary

Live-attenuated Rift Valley fever (RVF) vaccines replicate temporarily in the host, stimulating an innate and adaptive immune response. Neutralizing antibodies specific to the RVF virus (RVFV) are crucial for protection. Traditional live-attenuated RVF vaccines have been associated with adverse effects in gestating livestock. However, novel live-attenuated RVF vaccines with improved safety profiles are being developed and evaluated for use in animals and humans. These next-generation vaccines offer opportunities to improve global health.