Orf virus (ORFV), the prototype species of the parapoxvirus genus, is the causative agent of
contagious ecthyma, an extremely devastating
skin disease of sheep, goats, and humans that causes enormous economic losses in livestock production. ORFV is known for its ability to repeatedly infect both previously infected and vaccinated sheep due to several immunomodulatory genes encoded by the virus that temporarily suppress host immunity. Therefore, the development of novel, safe and effective
vaccines against ORFV
infection is an important priority. Although, the commercially licensed live-
attenuated vaccines have provided partial protection against ORFV
infections, the attenuated viruses have been associated with major safety concerns. In addition to safety issues, the persistent
reinfection of vaccinated animals warrants the need to investigate several factors that may affect
vaccine efficacy. Perhaps, the reason for the failure of the
vaccine is due to the long-term adaptation of the virus in tissue culture. In recent years, the development of
vaccines against ORFV
infection has achieved great success due to technological advances in
recombinant DNA technologies, which have opened a pathway for the development of
vaccine candidates that elicit robust immunity. In this review, we present current knowledge on immune responses elicited by ORFV, with particular attention to the effects of the viral
immunomodulators on the host immune system. We also discuss the implications of strain variation for the development of rational
vaccines. Finally, the review will also aim to demonstrate future strategies for the development of safe and efficient
vaccines against ORFV
infections.