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Therapeutic immunomodulation using a virus—the potential of inactivated orf virus

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Abstract

Viruses can manipulate the immune response against them by various strategies to influence immune cells, i.e. by over-activation leading to functional inactivation, bypassing antigen presentation or even suppression of effector functions. Little is known, however, about how these features of immune regulation and modulation could be used for therapeutic purposes. Reasons for this include the complexity of immune regulatory mechanisms under certain disease conditions and the risks that infections with viruses pose to human beings. The orf virus (ORFV), a member of the Parapoxvirus genus of the poxvirus family, is known as a common pathogen in sheep and goats worldwide. The inactivated ORFV, however, has been used as a preventative as well as therapeutic immunomodulator in veterinary medicine in different species. Here, we review the key results obtained in pre-clinical studies or clinical studies in veterinary medicine to characterise the therapeutic potential of inactivated ORFV. Inactivated ORFV has 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 inactivated ORFV has been recognised in several difficult-to-treat disease areas, such as chronic viral diseases, liver fibrosis or various forms of cancer. Further research will be required in order to evaluate the full beneficial potential of inactivated ORFV for therapeutic immunomodulation.

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Conflict of interest

O.W. is an employee of Bayer. O.W., A.A.M. and H.-D.V. are co-inventors of patent applications on the use of ORFV virus. A.F. and P.K. declare that they have no conflict of interest.

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Authors and Affiliations

  1. Bayer HealthCare AG, Leverkusen, Germany

    O. Weber

  2. Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand

    A. A. Mercer

  3. LWL University Hospital, Ruhr University Bochum, Bochum, Germany

    A. Friebe

  4. Institute of Molecular Medicine and Experimental Immunology, University Hospital Bonn, Bonn, Germany

    P. Knolle

  5. Institute of Medical Immunology and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité—Medical University Berlin, Berlin, Germany

    H.-D. Volk

  6. Bayer Pharmaceuticals Global Drug Discovery, Bayer HealthCare AG, 42096, Wuppertal, Germany

    O. Weber

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Weber, O., Mercer, A.A., Friebe, A. et al. Therapeutic immunomodulation using a virus—the potential of inactivated orf virus. Eur J Clin Microbiol Infect Dis 32, 451–460 (2013). https://doi.org/10.1007/s10096-012-1780-x

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