Immunomodulatory Strategies for Parapoxvirus: Current Status and Future Approaches for the Development of Vaccines against Orf Virus Infection

Abstract

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.

Recent advances in diagnostic approaches for orf virus

“…Clinically, ORFV infection mainly causes proliferative lesions on the skin of lips, oral mucosa, gums, tongues, and nostrils. As the disease progresses, erythema, vesicles, pustules, and scabs develop (Bukar et al 2021;Wang et al 2019a, b, c). It is difficult to differentiate ORFV from foot and mouth disease, bluetongue disease, peste des petits ruminants, and goat pox or sheep pox which cause similar clinical signs (Chu et al 2011;Gelaye et al 2016).…”

“…The absence of ORFV-specific neutralizing antibodies in previously infected animals may be the main reason why hosts can be repeatedly infected (Koptopoulos et al 1982). Furthermore, the ability of ORFV to repeatedly infect previously infected animals is largely attributed to multiple immunomodulatory proteins encoded by the virus that escape from host immune response (Bukar et al 2021).…”

Poxvirus-driven human diseases and emerging therapeutics

“…Animal bites and contact with recently vaccinated animals could also result in Orf since the most widely used veterinary Orf virus vaccines contain live, attenuated virus. 80 , 81 …”

“…Animal bites and contact with recently vaccinated animals could also result in Orf since the most widely used veterinary Orf virus vaccines contain live, attenuated virus. 80,81 Human to human transmission is not known to occur. Clinical disease may begin after an incubation period of 3 to 5 days as an erythematous macule progressing to form papules which may have a target-like appearance.…”

Poxvirus Driven Human Diseases and Emerging Therapeutics

“…Human pursuits that may place one at risk include, rearing sheep and goats (including bottle feeding and grooming), petting infected animals and having contact with contaminated material such as an animal harness. Animal bites and contact with recently vaccinated animals could also result in Orf since the most widely used veterinary Orf virus vaccines contain live, attenuated virus (80,81).…”