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.
Highlights
Small ruminants are of great economic importance to humans as they provide a tremendous source of protein, calcium, vitamins, fiber, hides, and especially wool for hundreds of millions of people worldwide
Orf virus (ORFV), the prototype species of the genus Parapoxvirus in the family Poxviridae causes highly contagious skin lesions popularly known as orf in several species of small ruminant sheep and goats [17,25,26,27,28,29,30], it can infect humans [31,32,33,34]
Recent studies demonstrated that the goats vaccinated with live-attenuated vaccines did not provide complete protection against ORFV infection when exposed to another ORFV strain derived from goats [124]
Summary
Small ruminants are of great economic importance to humans as they provide a tremendous source of protein, calcium, vitamins, fiber, hides, and especially wool for hundreds of millions of people worldwide. The central conserved genomic region of ORFV accounts for approximately 80% of the entire genome which is responsible for viral replication, transcription, and morphogenesis [32,54,63,105,106,107,108] It is well-documented that major immunogenic proteins located within the conserved region B2L (ORFV011) and F1L (ORFV059), are exploited prophylactically as vaccines against ORFV infections [78,109]. The review will seek to demonstrate new strategies and future approaches for the development of efficacious vaccines to control ORFV infections Such challenges can be addressed through careful observation and the use of recent advances in molecular biology to fill the existing knowledge gaps. The activated T-cell immunity could not destroy this antigens because the virus releases several virulence factors that prevent possible neutralization of the virion particles, as shown in Figure 2 [122]
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