Development of effective rift valley fever vaccines for use in sheep and humans. (360G-Wellcome-098635_Z_12_Z)

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that invariably causes death of newborn lambs and abortion in pregnant ewes. Human disease follows close contact with infected animal tissue and body fluids and is characterized by a mild febrile illness that occasionally progresses to a life-threatening haemorrhagic syndrome. No licensed vaccine is available for human use and that used in livestock is not safe for use in pregnant animals. Thus, the proposed research aims to develop a re combinant viral-vectored vaccine for use in sheep and humans. The RVF viral glycoproteins, Gn and Gc, that are targets of neutralizing antibodies, will be inserted into modified vaccinia virus Ankara (MVA) and a simian adenovirus (ChAdOx1) vector. These MVA-GnGc and ChAdOx1-GnGc vaccine constructs will then be assessed for immunogenicity in mice and the regimen yielding the highest neutralizing antibody titre identified. Finally, this regimen will be tested for efficacy against RVF in immunized sheep challenged intravenously with a virulent RVFV isolate. If protective, the immunization regimen will form the basis of a future sheep vaccine and provide proof-of-concept for human clinical trials.