Current Topics in Microbiology and Immunology Volume 332 Series Editors Richard W. Compans Emory University School of Medicine, Department of Microbiology and Immunology, 3001 Rollins Research Center, Atlanta, GA 30322, USA Max D. Cooper Department of Pathology and Laboratory Medicine, Georgia Research Alliance, Emory University, 1462 Clifton Road, Atlanta, GA 30322, USA Yuri Y. Gleba ICON Genetics AG, Biozentrum Halle, Weinbergweg 22, Halle 6120, Germany Tasuku Honjo Department of Medical Chemistry, Kyoto University, Faculty of Medicine, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan Hilary Koprowski Thomas Jefferson University, Department of Cancer Biology, Biotechnology Foundation Laboratories, 1020 Locust Street, Suite M85 JAH, Philadelphia, PA 19107-6799, USA Bernard Malissen Centre d’Immunologie de Marseille-Luminy, Parc Scientifique de Luminy, Case 906, Marseille Cedex 9 13288, France Fritz Melchers Biozentrum, Department of Cell Biology, University of Basel, Klingelbergstr. 50–70, 4056 Basel Switzerland Michael B.A. Oldstone Department of Neuropharmacology, Division of Virology, The Scripps Research Institute, 10550 N. Torrey Pines, La Jolla, CA 92037, USA Sjur Olsnes Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello 0310 Oslo, Norway Peter K. Vogt The Scripps Research Institute, Dept. of Molecular & Exp. Medicine, Division of Oncovirology, 10550 N. Torrey Pines. BCC-239, La Jolla, CA 92037, USA Alexander V. Karasev Editor Plant-produced Microbial Vaccines Editor Alexander V. Karasev University of Idaho Department of Plant, Soil & Entomological Sciences Moscow ID 83844-2339 USA [email protected] ISBN 978-3-540-70857-5 e-ISBN 978-3-540-70868-1 DOI 10.1007/978-3-540-70868-1 Current Topics in Microbiology and Immunology ISSN 0070-217x Library of Congress Catalog Number: 2008936144 © 2009 Springer-Verlag Berlin Heidelberg This work is subject to copyright. All rights reserved, whether the whole or part of the m aterial is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. 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Cover design: WMX Design Gmbh, Heidelberg Printed on acid-free paper 9 8 7 6 5 4 3 2 1 springer.com Preface In recent years, plants have been increasingly explored for the production of bio- medicines and vaccine components. The two main advantages of plant systems are low cost and a greater potential for scalability as compared to microbial or animal systems. An additional advantage from the public health point of view is the high safety compared to animal systems, which is important for vaccine production: there are no known plant pathogens capable of replicating in animals and in humans, in particular. A particular antigen or a protein has to be expressed in a plant using one of the many available platforms; this antigen/protein subsequently needs to be purified or processed, and later formulated into a vaccine or a therapeutic; these need to be delivered to a human or animal body via an appropriate route. Naturally, all these vaccines and therapeutics must be subjected to regulatory approvals prior to their use. Thus, the challenge is to adapt plant-based platforms for the production of cost-efficient biomedicals that can be approved by FDA for use as vaccine components or therapeutics, which will be competitive against exist- ing vaccines and drugs. This volume attempts to address the entire spectrum of challenges facing the nascent field of plant-based biomedicals, from the selection of an appropriate pro- duction platform to specific methods of downstream processing and regulatory approval issues. The chapter by D.C. Hooper is devoted to immunological issues that can arise for antigens produced in plants and delivered to a human or an animal via different routes. This chapter also discusses such specific topics as tolerance and immunomodulation, with particular reference to oral delivery of plant pro- duced antigens. The chapter by Smith et al. discusses one specific example of a virus-based platform for the expression of peptides in plants, and related issues of downstream processing, that is, manufacture and purification of virus particle- based vaccines, and final product release and stability. Another production plat- form, via chloroplast-based expression of proteins, is discussed in the chapter by S. Chebolu and H. Daniell. The chapter presents several examples of various vac- cine components and other biomedicals produced in plants, and these range from bacterial and viral proteins to human serum proteins and antibodies. The chapter by Ko et al. describes a particular application of the plant-based production of human antibodies used for passive immunization against rabies. It is an example of a clas- sical transgenic technology modified for a specific expression of two antibody v vi Preface chains. The chapter by R. Hammond and L. Nemchinov reviews the current status of plant production of veterinary vaccines, utilizing a great variety of platforms. The final chapter by C. Tacket presents case studies for the human trials of the first plant-produced candidate vaccines and discusses several regulatory issues that need to be addressed prior to their approval. Production of vaccine components and other biomedicals in plants has a great potential in medicine and veterinary science. We hope that this volume will be a valuable contribution to this rapidly growing research field. USA A.V. Karasev Contents Plant Vaccines: An Immunological Perspective .......................................... 1 D.C. Hooper Display of Peptides on the Surface of Tobacco Mosaic Virus Particles ................................................................................................ 13 M.L. Smith, W.P. Fitzmaurice, T.H. Turpen, and K.E. Palmer Chloroplast-Derived Vaccine Antigens and Biopharmaceuticals: Expression, Folding, Assembly and Functionality ...................................... 33 S. Chebolu and H. Daniell Production of Antibodies in Plants: Approaches and Perspectives .............................................................................................. 55 K. Ko, R. Brodzik, and Z. Steplewski Plant Production of Veterinary Vaccines and Therapeutics ....................... 79 R. W. Hammond and L. G. Nemchinov Plant-Based Oral Vaccines: Results of Human Trials ................................ 103 C.O. Tacket Index ................................................................................................................. 119 vii Contributors Robert Brodzik Biotechnology Foundation Labs, Thomas Jefferson University, Philadelphia, PA 19107, USA S. Chebolu University of Central Florida, Department of Molecular Biology & Microbiology, 336 Biomolecular Science (Bldg # 20), Orlando FL 32816-2360, USA [email protected] Henry Daniell University of Central Florida, Department of Molecular Biology & Microbiology, 336 Biomolecular Science (Bldg # 20), Orlando FL 32816-2360, USA Wayne P. Fitzmaurice Large Scale Biology Corporation, Vacaville, CA 95688, USA Rosemarie W. Hammond USDA-ARS, BARC-West, Rm.252, Bldg. 011, Beltsville, MD20705, USA Craig Hooper Associate Professor, Center for Neurovirology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA [email protected] Alexander V. Karasev University of Idaho, Department of PSES, Moscow, ID 83844-2339, USA [email protected] Kisung Ko Department of Biologcal Science, College of Natural Sciences, Wonkwang University, Iksan, Jeonbuk 570-749, Korea [email protected] Lev G. Nemchinov USDA-ARS, BARC-West, Rm.252, Bldg. 011, Beltsville, MD20705, USA [email protected] ix x Contributors Kenneth E. Palmer Owensboro Cancer Research Program, University of Louisville, 1020 Breckenridge Street, Owensboro, KY 42303, USA [email protected] Mark L. Smith Large Scale Biology Corporation, Vacaville, CA 95688, USA Zeonon Steplewski Biotechnology Foundation Labs, Thomas Jefferson University, Philadelphia, PA 19107, USA Carol O. Tacket Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore St., Baltimore, MD 21201-1192 [email protected] Thomas H. Turpen Technology Innovation Group, Inc., 7006 Firewheel Hollow, Austin, TX 78750, USA [email protected] Plant Vaccines: An Immunological Perspective D. C. Hooper Contents Introduction ............................................................................................................................... 2 Basic Immunology: Antigens and Immunogenicity ................................................................. 3 Possible Advantages and Limitations of Using Plants to Produce Reagents for Active Vaccination .................................................................................................................... 4 Plants as Expression Vectors ................................................................................................ 4 Plant Viruses and Bacteria as Expression Vectors ................................................................ 4 Basic Immunology: Routes of Vaccine Administration ............................................................ 6 Enhancing Immunogenicity of a Potential Plant Vaccine Versus the Risk of Breaking Tolerance to Food Antigens ....................................................................................... 7 Strategies to Make Antigens Expressed by Plants More Immunogenic............................... 7 Risks of Breaking Tolerance ................................................................................................ 8 Other Uses of Plant-Based Immunological Reagents ............................................................... 8 Immunomodulation .............................................................................................................. 8 Production of Antibodies for Passive Immunization in Plants ............................................. 9 Conclusions ............................................................................................................................... 9 References ................................................................................................................................. 10 Abstract The advent of technologies to express heterologous proteins in planta has led to the proposition that plants may be engineered to be safe, inexpensive vehicles for the production of vaccines and possibly even vectors for their delivery. The immunogenicity of a variety of antigens of relevance to vaccination expressed in different plants has been assessed. The purpose of this article is to examine the utility of plant-expression systems in vaccine development from an immunological perspective. D.C. Hooper((cid:2)) Center for Neurovirology , Kimmel Cancer Center , Thomas Jefferson University, Philadelphia , PA 19107-6731 , USA e-mail: [email protected] A.V. Karasev (ed.) Plant-produced Microbial Vaccines. 1 Current Topics in Microbiology and Immunology 332 © Springer-Verlag Berlin Heidelberg 2009