Inactivated Orf-virus shows disease modifying antiviral activity in a guinea pig model of genital herpesvirus infection

Abstract

Background: Inactivated Orf virus (iORFV) has been used as a preventative as well as a therapeutic immunomodulator in veterinary medicine in different species. iORFV elicits strong effects on cytokine secretion in mice and human immune cells leading to an auto-regulated loop of initial up-regulation of inflammatory and Th1-related cytokines followed by Th2-related cytokines that attenuate immunopathology. The therapeutic potential of iORFV has been recognized in several models for difficult-to-treat disease areas such as chronic viral diseases, liver fibrosis or various forms of cancer. Methods: Guinea pigs were infected with Human Herpesvirus (HSV)-2 strain MS and treated with iORFV, Acyclovir (ACV) or placebo, respectively. Clinical score of herpes lesions and viral shedding was assessed over a period of 40 days. In addition, viral DNA in dorsal root ganglia was quantified at the end of the study. Results: Disease symptoms were minimal or absent in iORFV-treated guinea pigs but tended to be severe in animals treated with either ACV or placebo. The cumulated disease score was significantly reduced in iORFV-treated but not in ACV- or placebo-treated guinea pigs. In addition, treatment with iORFV, but not ACV or placebo, led to significant reduction of viral DNA load in dorsal root ganglia. Conclusion: iORFV effectively suppressed recurrences in guinea pigs experimentally infected with HSV. iORFV did not only reduce recurrent disease episodes but was, compared with ACV, more effective in reducing latency as measured by viral DNA detected in dorsal root ganglia of infected animals. Keywords: Immunotherapy, Immunomodulation, Orf virus, Herpesvirus, Recurrent genital herpes disease