Establishment of an advanced preclinical model for Rift Valley fever (RVF) virus for the assessment of vaccine efficacy and licensure pathway via the Animal Rule.

NOTE THAT THERE IS NO CHANGE TO PROJECT SCOPE BUT THERE WAS NO OPTION IN THE PCR LIST TO DO A CHANGE TO DATES IN MILESTONES. Rift Valley fever (RVF) is an acute viral haemorrhagic fever that is most commonly seen in domesticated animals -- such as cattle, buffalo, sheep, goats and camels -- and can cause illness in people. Humans can get infected with RVF virus though contact with blood, body fluids, or tissues of infected animals, or through bites from infected mosquitoes. There are currently no human vaccines available against RVF virus. Due to being recognised as a priority pathogen by the UK Vaccine Network (UKRN), World Health Organisation (WHO) and the Coalition for Epidemic Preparedness Innovations (CEPI), there are substantial efforts into vaccine development for RVF virus. In addition, due to causing disease in livestock, animal vaccines are also being developed. These efforts are allowing a plethora of candidates to progress forwards through preclinical models with small animals and ruminants and into Phase I and II clinical trials. However, for licensure, regulated studies demonstrating efficacy are required. The usual route would be via Phase III trials, but due to the sporadic and unpredictable nature of RVF outbreaks, it is widely accepted that this will be difficult. Therefore, a viable option would be to demonstrate efficacy via the Animal Rule, introduced by the US Food and Drug Administration as a route for licensure where human trials are not ethical or feasible, such as RVF. The Animal Rule stipulates that efficacy testing needs to be performed in two species, with one as close to human disease as possible. This project will therefore establish an advanced preclinical model of RVF virus infection at the UK Health Security Agency (UKHSA). This funding will be able to exploit the expertise of _in vivo_ modelling with high containment pathogens available within UKHSA and ensure that research is conducted to some of the highest welfare standards in the world. Previous work on advanced models at UKHSA has been used to support licensure of vaccine and therapeutics, so the regulatory infrastructure for conduction of studies to the required quality standards are in place and established. Following the completion of this stream 1 project, advanced preclinical testing capacity for promising vaccine candidates will be available and fill the void after the initial stages of clinical evaluation. This will allow the final licensure of vaccines, enabling strategic and coherent responses to future outbreaks of RVF.