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Pathogen-Derived Immunomodulatory Molecules pp 132–156Cite as

The Serpin Saga; Development of a New Class of Virus Derived Anti-Inflammatory Protein Immunotherapeutics

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 666))

Abstract

Serine proteinase inhibitors, also called serpins, are an ancient grouping of proteins found in primitive organisms from bacteria, protozoa and horseshoe crabs and thus likely present at the time of the dinosaurs, up to all mammals living today. The innate or inflammatory immune system is also an ancient metazoan regulatory system, providing the first line of defense against infection or injury. The innate inflammatory defense response evolved long before acquired, antibody dependent immunity. Viruses have developed highly effective stratagems that undermine and block a wide variety of host inflammatory and immune responses. Some of the most potent of these immune modifying strategies utilize serpins that have also been developed over millions of years, including the hijacking by some viruses for defense against host immune attacks. Serpins represent up to 2–10 percent of circulating plasma proteins, regulating actions as wide ranging as thrombosis, inflammation, blood pressure control and even hormone transport. Targeting serpin-regulated immune or inflammatory pathways makes evolutionary sense for viral defense and many of these virus-derived inhibitory proteins have proven to be highly effective, working at very low concentrations—even down to the femptomolar to picomolar range. We are studying these viral anti-inflammatory proteins as a new class of immunomodulatory therapeutic agents derived from their native viral source. One such viral serpin, Serp-1 is now in clinical trial (conducted by VIRON Therapeutics, Inc.) for acute unstable coronary syndromes (unstable angina and small heart attacks), representing a ’first in class’ therapeutic study. Several other viral serpins are also currendy under investigation as anti-inflammatory or anti-immune therapeutics. This chapter describes these original studies and the ongoing analysis of viral serpins as a new class of virus-derived immunotherapeutic.

Wisdom in infinite thought, Expanding time, endlessly sought, An ancient star journeying here So far, so near, bright seer This unseen dance A brilliant chance —Anonymous

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Authors and Affiliations

  1. Department of Medicine, University of Florida, Gainesville, Florida, USA

    Alexandra Lucas, Liying Liu, Erbin Dai, Ganesh Munuswamy-Ramunujam, Jennifer A. Davids, Mee Y. Bartee & Grant McFadden

  2. Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA

    Alexandra Lucas, Ganesh Munuswamy-Ramunujam, Jennifer A. Davids, Mee Y. Bartee, Mary Richardson, Collin Sullivan, Richard Moyer & Grant McFadden

  3. Robarts Research Institute, University of Western Ontario, London, Ontario, Canada

    Alexandra Lucas, Liying Liu, Erbin Dai & Mark Poznansky

  4. University of Maastricht, Maastricht, The Netherland

    Ilze Bot, Robert Zhong, Leslie Miller & Erik Biessen

  5. Oregon Health Sciences University, Portland, Oregon, USA

    Kasinath Viswanathan

  6. University of Oklahoma, Oklahoma City, Oklahoma, USA

    Jakob Richardson & Alexander Christov

  7. Oregon Health Sciences University, Portland, Oregon, USA

    Hao Wang

  8. Viron Therapeutics, Inc, London, Ontario, Canada

    Colin Macaulay

  9. McMaster University, Hamilton, Ontario, Canada

    Mark Hatton

  10. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK

    David A. Lomas

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  1. Alexandra Lucas
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Corresponding author

Correspondence to Alexandra Lucas .

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Editors and Affiliations

  1. Inflammation and Immunity Group, Institute of Molecular Medicine, Trinity College, Dublin, Ireland

    Padraic G. Fallon BSc, MSc, PhD

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© 2009 Landes Bioscience and Springer Science+Business Media

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Lucas, A. et al. (2009). The Serpin Saga; Development of a New Class of Virus Derived Anti-Inflammatory Protein Immunotherapeutics. In: Fallon, P.G. (eds) Pathogen-Derived Immunomodulatory Molecules. Advances in Experimental Medicine and Biology, vol 666. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1601-3_11

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