Table of Contents

Volume 7, Issue 3

  March 2011

  Pages 285 - 390

Special Issue on Plant-derived Vaccines

Guest Editor Dr. Maxim Golovkin, Thomas Jefferson University, Philadelphia; PA, USA

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva M. Riedmann
Page 285
http://dx.doi.org/10.4161/hv.7.3.15349
Abstract | PDF







NEWS, POLICY AND PROFILES

Open Access Article

News

Eva M. Riedmann
Pages 286 - 289
http://dx.doi.org/10.4161/hv.7.3.15351
Abstract | PDF


Some vaccines may protect against childhood cancers
GSK malaria vaccine offers long-lasting protection
Cholera vaccination post-outbreak: Still beneficial
Prescrire takes a close look at Wyeth’s Prevnar 13
Chilean scientists develop alcoholism vaccine
No association of H1N1 vaccine with Guillain-Barre
New vaccine to help polio eradication
H1N1 infection provides clues to universal flu vaccine


Open Access Article

High time for GAVI to push for lower prices

Daniel Berman and Rohit Malpani
Page 290
http://dx.doi.org/10.4161/hv.7.3.15218
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

Beyond patents: The GAVI Alliance, AMCs and improving immunization coverage through public sector vaccine production in the global south

Anne-Emanuelle Birn and Joel Lexchin
Pages 291 - 292
http://dx.doi.org/10.4161/hv.7.3.15217
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

The pilot AMC: The acceptance of policy evolution

Jim Dobbins, Lord Avebury and Hugh McKinney
Page 293
http://dx.doi.org/10.4161/hv.7.3.15361
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

Diverse tools needed to ensure affordable vaccines for the poor

Christopher J. Elias
Page 294
http://dx.doi.org/10.4161/hv.7.3.15360
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

Fixing GAVI’s cash crunch

Andrew Farlow
Pages 295 - 296
http://dx.doi.org/10.4161/hv.7.3.15359
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

Getting priorities straight

Richard T. Mahoney
Page 297
http://dx.doi.org/10.4161/hv.7.3.15215
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

New vaccines for the least developed countries

Mark Kane
Pages 298 - 299
http://dx.doi.org/10.4161/hv.7.3.15216
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

The AMC is helping save children’s lives today

Nina Schwalbe
Pages 300 - 301
http://dx.doi.org/10.4161/hv.7.3.15357
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/

Open Access Article

Why the AMC matters

Frederick Were
Page 302
http://dx.doi.org/10.4161/hv.7.3.15355
Abstract | PDF

Comments on Donald Light's article from previous issue. http://www.landesbioscience.com/journals/vaccines/article/14919/




EDITOR'S CORNER

Open Access Article

Plant biotechnology for production of recombinant pharmaceuticals

Maxim Golovkin
Pages 303 - 304
http://dx.doi.org/10.4161/hv.7.3.15350
Abstract | PDF







REVIEWS

Open Access Article

Tobacco derived cancer vaccines for non-Hodgkin’s lymphoma: Perspectives and progress

Alison A. McCormick
Pages 305 - 312
http://dx.doi.org/10.4161/hv.7.3.14163
Abstract | PDF

Everyone appreciates the irony of using tobacco plants to cure cancer.¹ Recently featured in a populist Wall Street Journal article,² the use of plants to produce medicinal products was presented as novel, even though we are decades into development of numerous products for specific medical applications (reviewed extensively in ^{3, 4}). Though the tobacco plant and its relatives offer a qualified set of advantages for producing complex biologicals, and in many cases overcome problems that plague traditional expression systems, FDA licensed products derived from bioengineered plants have yet to appear in the marketplace. Despite a difficult beginning, recent advances in plant biotechnology have been as cutting edge as those in the fields of molecular biology and chemical engineering, which now position the field for a new level of commercial relevance. The basis for this review is a description of the first FDA qualified parenterally administered vaccine clinical trial using a plant derived product. We have confirmed in this trial that plant proteins can be qualified to the same level as biologicals from other sources, and are safe when given as injected vaccines. Most importantly though, immune responses to plant proteins were seen in 66% of cancer patients, and these responses were to the desired antigenic determinants, not to xenogenic plant antigens. Problems and solutions that arose during the development of a safe and effective human vaccine are discussed.

Open Access Article

Clinical development of plant-produced recombinant pharmaceuticals: Vaccines, antibodies and beyond

Vidadi Yusibov, Stephen J. Streatfield and Natasha Kushnir
Pages 313 - 321
http://dx.doi.org/10.4161/hv.7.3.14207
Abstract | PDF

In the last few years, plants have become an increasingly attractive platform for recombinant protein production. This builds on two decades of research, starting with transgenic approaches to develop oral vaccines in which antigens or therapeutics can be delivered in processed plant biomass, and progressing to transient expression approaches whereby high yields of purified targets are administered parenterally. The advantages of plant-based expression systems include high scalability, low upstream costs, biocontainment, lack of human or animal pathogens, and ability to produce target proteins with desired structures and biological functions. Using transgenic and transient expression in whole plants or plant cell culture, a variety of recombinant subunit vaccine candidates, therapeutic proteins, including monoclonal antibodies, and dietary proteins have been produced. Some of these products have been tested in early phase clinical trials, and show safety and efficacy. Among those are mucosal vaccines for diarrheal diseases, hepatitis B and rabies; injectable vaccines for non-Hodgkin’s lymphoma, H1N1 and H5N1 strains of influenza A virus, and Newcastle disease in poultry; and topical antibodies for the treatment of dental caries and HIV. As lead plant-based products have entered clinical trials, there has been increased emphasis on manufacturing under current Good Manufacturing Practice (cGMP) guidelines, and the preparation and presentation to the relevant government agencies of regulatory packages.

Open Access Article

Safety of plant-made pharmaceuticals: Product development and regulatory considerations based on case studies of two autologous human cancer vaccines

Daniel Tusé
Pages 322 - 330
http://dx.doi.org/10.4161/hv.7.3.14213
Abstract | PDF

Guidelines issued by regulatory agencies for the development of plant-made pharmaceutical (PMP) products provide criteria for product manufacturing and characterization, safety determination, containment and mitigation of environmental risks. Features of plant-made products do not always enable an easy fit within the criteria subscribed to by regulators. The unconventional nature of plant-based manufacturing processes and peculiarities of plant biology relative to that of traditional biological production systems have led to special considerations in the regulatory scrutiny of PMP. Presented in this review are case studies of two plant-made autologous (patient-specific) cancer vaccines, the nature of which introduced challenges to conventional and standardized development and preclinical evaluation routes. The rationale presented to FDA by the sponsors of each vaccine to build consensus and obtain variances to existing guidelines is discussed. While development of many plant-made biologics can be accomplished within the existing regulatory framework, the development of specialized products can be defended with rational arguments based on strong science.

Open Access Article

Geminiviral vectors based on bean yellow dwarf virus for production of vaccine antigens and monoclonal antibodies in plants

Qiang Chen, Junyun He, Waranyoo Phoolcharoen and Hugh S. Mason
Pages 331 - 338
http://dx.doi.org/10.4161/hv.7.3.14262
Abstract | PDF

Expression of recombinant vaccine antigens and monoclonal antibodies using plant viral vectors has developed extensively during the past several years. The approach benefits from high yields of recombinant protein obtained within days after transient delivery of viral vectors to leaves of Nicotiana benthamiana, a tobacco relative. Modified viral genomes of both RNA and DNA viruses have been created. Geminiviruses such as bean yellow dwarf virus (BeYDV) have a small, single stranded DNA genome that replicates in the nucleus of an infected plant cell, using the cellular DNA synthesis apparatus and a virus-encoded replication initiator protein (Rep). BeYDV-derived expression vectors contain deletions of the viral genes encoding coat and movement proteins and insertion of an expression cassette for a protein of interest. Delivery of the geminiviral vector to leaf cells via Agrobacterium-mediated delivery produces very high levels of recombinant DNA that can act as a transcription template, yielding high levels of mRNA for the protein of interest. Several vaccine antigens, including Norwalk virus capsid protein and hepatitis B core antigen, were expressed using the BeYDV vector at levels up to 1mg per g of leaf mass. BeYDV replicons can be stacked in the same vector molecule by linking them in tandem, which enables production of multi-subunit proteins like monoclonal antibody (mAb) heavy and light chains. The protective mAb 6D8 against Ebola virus was produced at 0.5mg per g of leaf mass. Multi-replicon vectors could be conveniently used to produce protein complexes, e.g. virus-like particles that require two or more subunits.

Open Access Article

Vaccine farming in Cape Town

Edward P. Rybicki, Anna-Lise Williamson, Ann Meyers and Inga I. Hitzeroth
Pages 339 - 348
http://dx.doi.org/10.4161/hv.7.3.14263
Abstract | PDF

The review details the development of the Subunit Vaccine Group at the University of Cape Town, from its beginnings as a plant virology laboratory in the 1980s. The investigation and development of Human papillomavirus (HPV) and Human immunodeficiency vaccine candidates are covered in detail, with an emphasis on how this work allowed the evolution of a systematic approach to the optimisation of expression of these and other proteins especially in plants, but also in insect cell culture. We discuss various insights gained during our work, such as approaches to codon optimisation, use of different vector systems and plant hosts, intracellular targetting and gene modification. The future prospects for both our work and for the field of plant-made vaccines in general, are discussed.

Open Access Article

Emerging antibody products and Nicotiana manufacturing

Kevin J. Whaley, Andrew Hiatt and Larry Zeitlin
Pages 349 - 356
http://dx.doi.org/10.4161/hv.7.3.14266
Abstract | PDF

Antibody based products are not widely available to address multiple global health challenges due to high costs, limited manufacturing capacity, and long manufacturing lead times. Nicotiana-based manufacturing of antibody products may now begin to address these challenges as a result of revolutionary advances in transient expression and altered glycosylation pathways. This review provides examples of emerging antibody-based products (mucosal and systemic) that could be competitive and commercially viable when the attributes of Nicotiana-based manufacturing (large scale, versatile, rapid, low cost) are utilized.

Open Access Article

Seed-based oral vaccines as allergen-specific immunotherapies


Pages 357 - 366
http://dx.doi.org/10.4161/hv.7.3.14302
Abstract | PDF

Plant-based vaccines have advantages over conventional vaccines in terms of scalability, lack of requirement for cold chain logistics, stability, safety, cost-effectiveness and needle-free administration. In particular, when antigen is expressed in seeds, high production is possible and immunogenicity is not lost even if stocked at ambient temperature for several years. Induction of immune tolerance (desensitization) to allergen is a principle strategy for controlling allergic diseases, and is generally carried out by subcutaneous injection. Seed-based oral administration offers a straightforward and inexpensive alternative approach to deliver vaccines effectively to the GALT without loss of activity. Consumption of transgenic seeds containing modified hypo-allergenic tolerogen or T-cell epitope peptides derived from allergens has no or very few severe side effects and can induce immune tolerance leading to reduction of allergen-specific IgE production, T-cell proliferation and release of histamine. Suppression of allergen-specific clinical symptoms results. Thus, seed-based allergy vaccines offer an innovative and convenient allergen-specific immunotherapeutic approach as an alternative to conventional allergen-specific immunotherapy.

Open Access Article

Transgenic crops for the production of recombinant vaccines and anti-microbial antibodies

Jenny Peters and Eva Stoger
Pages 367 - 374
http://dx.doi.org/10.4161/hv.7.3.14303
Abstract | PDF

Plants can be used to produce inexpensive and highly immunogenic vaccines, particularly those aimed against mucosal pathogens. Several plant-derived vaccines have already completed early-phase clinical trials and many more are in the pipeline. The number of products in development has increased as the production technology itself has evolved, reflecting a better understanding of plant molecular biology, more sophisticated genetic engineering techniques, and more recently the development of tools and strategies to increase yields and engineer specific glycan groups on plant-derived glycoproteins. There are many different platforms including whole-plant transient expression systems based on Agrobacterium and/or plant viruses, contained systems based on cultured plant cells or aquatic plants, and stable transgenic plants expressing recombinant proteins in leaves, seeds, fruits or tubers/roots. Although the transient systems are rapid and high-yielding, stable transgenic plants are more scalable and may ultimately provide for more economical large-scale production, which was the original vision of ‘molecular farming’. Grain crops such as cereals and legumes are particularly valuable because recombinant proteins expressed in seeds are stable at ambient temperatures and any bioload can be reduced by surface sterilization. Seeds also present interesting formulation options, e.g. the use of seed-specific storage organelles for encapsulation and the slow release of mucosal vaccines. In this article, we review the current status and recent developments in the area of molecular farming in crop plants, focusing particularly on engineered seeds as production and delivery vehicles for recombinant vaccines and antibodies.

Open Access Article

Molecular pharming: Future targets and aspirations

Mathew Paul, Craig van Dolleweerd, Pascal M.W. Drake, Rajko Reljic, Harry Thangaraj, Tommaso Barbi, Elena Stylianou, Ilaria Pepponi, Leonard Both, Verena Hehle, Luisa Madeira, Varghese Inchakalody, Sammy Ho, Thais Guerra and Julian K-C. Ma
Pages 375 - 382
http://dx.doi.org/10.4161/hv.7.3.14456
Abstract | PDF

Molecular Pharming represents an unprecedented opportunity to manufacture affordable modern medicines and make these available at a global scale. The area of greatest potential is in the prevention of infectious diseases, particular in underdeveloped countries where access to medicines and vaccines has historically been limited. This is why, at St. George’s, we focus on diseases such as HIV, TB and rabies, and aim to develop production strategies that are simple and potentially easy to transfer to developing countries.

Open Access Article

Recent advances of Cowpea mosaic virus-based particle technology

Nicholas P. Montague, Eva C. Thuenemann, Pooja Saxena, Keith Saunders, Paolo Lenzi and George P. Lomonossoff
Pages 383 - 390
http://dx.doi.org/10.4161/hv.7.3.14989
Abstract | PDF

Particles of cowpea mosaic virus (CPMV) have enjoyed considerable success as a means of presenting peptides for vaccine purposes. However, the existing technology has limitations in regard to the size and nature of the peptides which can be presented and has problems regarding bio-containment. Recent developments suggest ways by which these problems can be overcome, increasing the range of potential applications of CPMV-based particle technology.