Orf virus (ORFV) is an epitheliotropic, double-stranded DNA pathogen belonging to the genus Parapoxvirus, and it is the causative agent of contagious ecthyma (CE) in small ruminants. It is an endemic disease on goat and sheep herds around the world. It is often a neglected disease, with impacts on herd health and productivity, while also being an occupational zoonosis. This review explores the causative agent of ovine ecthyma, its epidemiology, and clinical manifestations, with a particular emphasis on its interaction with the host's immune system and the development of ORFV vaccines. Like other members of the Poxviridae family, ORFV expresses numerous immunomodulatory genes, which complicate vaccination efforts and disease management. This review highlights the challenges posed by ORFV in achieving effective immunization and discusses potential vaccine strategies to overcome these obstacles.

01 Jun 2024·Veterinary Microbiology

Orf virus as an adjuvant enhances the immune response to a PCV2 subunit vaccine

Article

Author: Chen, Longfei ; Xiao, Shaobo ; Sun, Jie ; Ma, Jun ; Fang, Liurong ; Xiao, Xun

Orf virus (ORFV), a member of the genus Parapoxvirus, possesses an excellent immune activation capability, which makes it a promising immunomodulation agent. In this study, we evaluated ORFV as a novel adjuvant to enhance the immune response of mice to a subunit vaccine using porcine circovirus type 2 (PCV2) capsid (Cap) protein as a model. Our results showed that both inactivated and live attenuated ORFV activated mouse bone marrow-derived dendritic cells and increased expression of immune-related cytokines interleukin (IL)-1β, IL-6, and TNF-α. Enhanced humoral and cellular immune responses were induced in mice immunized with PCV2 Cap protein combined with inactivated or live attenuated ORFV adjuvant compared with the aluminum adjuvant. Increased secretion of Th1 and Th2 cytokines by splenic lymphocytes in immunized mice further indicated that the ORFV adjuvant promoted a mixed Th1/Th2 immune response. Moreover, addition of the ORFV adjuvant to the PCV2 subunit vaccine significantly reduced the viral load in the spleen and lungs of PCV2-challenged mice and prevented pathological changes in lungs. This study demonstrates that ORFV enhances the immunogenicity of a PCV2 subunit vaccine by improving the adaptive immune response, suggesting the potential application of ORFV as a novel adjuvant.

01 Dec 2023·Molecular Therapy - Oncolytics

Kinetic analysis of oncolytic OrfV-induced innate and adaptive immune responses in a murine model of late-stage ovarian cancer

Article

Author: Goens, Melanie M ; Wood, Geoffrey A ; Petrik, James J ; Wootton, Sarah K ; Pereira, Madison ; Minott, Jessica A ; Bridle, Byram W ; Karimi, Khalil ; Santry, Lisa A ; Viloria-Petit, Alicia M ; Yates, Jake G E ; Matuszewska, Kathy ; van Vloten, Jacob P

Immunotherapies revive host immune responses against tumors by stimulating innate and adaptive immune effector cells with antitumor functions. Thus, detailed studies of immunological cell phenotypes and functions within the tumor microenvironment (TME) following immunotherapy treatments is critical to identifying the determinants of therapeutic success, optimizing treatment regimens, and driving curative outcomes. Oncolytic viruses such as Orf virus (OrfV) are multifunctional biologics that preferentially infect and kill cancer cells while simultaneously causing inflammation that drives anticancer immune responses. Here, we describe the immunological impact of OrfV on the ascites TME in a preclinical model of advanced-stage epithelial ovarian cancer. OrfV promoted the infiltration of several immune effector cells with increased expression of activation markers and effector cytokines into the ascites TME, which correlated with reduced ascites tumor burden and improved survival. The kinetics of the immune response and change in tumor burden following OrfV therapy revealed an optimal re-administration time to sustain antitumor immunity, further extending survival. The data presented highlight the importance of investigating immune response kinetics following immunotherapy and demonstrate that detailed kinetic profiling of immune responses can reveal novel insights into mechanisms of action that can guide the development of more effective therapies.

100 Deals associated with ORFV (Jilin University)

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Preclinical	China	Jilin University	14 Jan 2023

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