Wildlife are a reservoir of diseases affecting both humans and domestic animals. These wildlife reservoirs represent a potential threat to public health, serving as a continuous and difficult to eradicate source of infection for zoonotic diseases, but may also represent a significant economic threat to US agriculture. In particular, wild ruminants including white-tail deer may harbor vector-borne infectious diseases that can directly impact US Cattle and Sheep operations. Medgene Labs focuses on the development of novel subunit vaccine formulations to address these critical diseases that may affect both public health and US agricultural animals. Subunit vaccines have the advantage of being highly stable and safe from potential reversion to virulence, supporting strong protective immune responses without the potential for contributing to new outbreaks through combination with wild-type agents. Furthermore, these strategies are ideally suited to the development of immune responses to effectively differentiate vaccinated from infected animals (DIVA approach). Our current development efforts have defined highly efficacious, DIVA-compatible vaccine formulation directed against Rift Valley Fever Virus, and a focus of this proposal is to define an efficacious oral vaccine. This proposal will leverage the existing strength that Medgene Labs brings to the generation of highly effective and safe vaccine strategies directed against RVFV and other orbiviruses of national interest to define appropriate delivery systems for oral vaccination of wildlife. Following initial characterization of these oral formulations in a well-established sheep model, we will proceed directly in Phase II to define efficacy in target cervid populations for use in wild ruminants.