Production Of Vaccines In Plants Research Articles

Plant-made vaccines against viral diseases in humans and farm animals.

Plants provide not only food and feed, but also herbal medicines and various raw materials for industry. Moreover, plants can be green factories producing high value bioproducts such as biopharmaceuticals and vaccines. Advantages of plant-based production platforms include easy scale-up, cost effectiveness, and high safety as plants are not hosts for human and animal pathogens. Plant cells perform many post-translational modifications that are present in humans and animals and can be essential for biological activity of produced recombinant proteins. Stimulated by progress in plant transformation technologies, substantial efforts have been made in both the public and the private sectors to develop plant-based vaccine production platforms. Recent promising examples include plant-made vaccines against COVID-19 and Ebola. The COVIFENZ® COVID-19 vaccine produced in Nicotiana benthamiana has been approved in Canada, and several plant-made influenza vaccines have undergone clinical trials. In this review, we discuss the status of vaccine production in plants and the state of the art in downstream processing according to good manufacturing practice (GMP). We discuss different production approaches, including stable transgenic plants and transient expression technologies, and review selected applications in the area of human and veterinary vaccines. We also highlight specific challenges associated with viral vaccine production for different target organisms, including lower vertebrates (e.g., farmed fish), and discuss future perspectives for the field.

Recent Progress on Vaccines Produced in Transgenic Plants.

The development of vaccines from plants has been going on for over two decades now. Vaccine production in plants requires time and a lot of effort. Despite global efforts in plant-made vaccine development, there are still challenges that hinder the realization of the final objective of manufacturing approved and safe products. Despite delays in the commercialization of plant-made vaccines, there are some human vaccines that are in clinical trials. The novel coronavirus (SARS-CoV-2) and its resultant disease, coronavirus disease 2019 (COVID-19), have reminded the global scientific community of the importance of vaccines. Plant-made vaccines could not be more important in tackling such unexpected pandemics as COVID-19. In this review, we explore current progress in the development of vaccines manufactured in transgenic plants for different human diseases over the past 5 years. However, we first explore the different host species and plant expression systems during recombinant protein production, including their shortcomings and benefits. Lastly, we address the optimization of existing plant-dependent vaccine production protocols that are aimed at improving the recovery and purification of these recombinant proteins.

Plant-Derived Human Vaccines: Recent Developments.

The idea of producing vaccines in plants originated in the late 1980s. Initially, it was contemplated that this notion could facilitate the concept of edible vaccines, making them more cost effective and easily accessible. Initial studies on edible vaccines focussed on the use of a variety of different transgenic plant host species for the production of vaccine antigens. However, adequate expression levels of antigens, the difficulties predicted with administration of consistent doses, and regulatory rules required for growth of transgenic plants gave way to the development of vaccine candidates that could be purified and administered parenterally. The field has subsequently advanced with improved expression techniques including a shift from using transgenic to transient expression of antigens, refinement of purification protocols, a deeper understanding of the biological processes and a wealth of evidence of immunogenicity and efficacy of plant-produced vaccine candidates, all contributing to the successful practice of what is now known as biopharming or plant molecular farming. The establishment of this technology has resulted in the development of many different types of vaccine candidates including subunit vaccines and various different types of nanoparticle vaccines targeting a wide variety of bacterial and viral diseases. This has brought further acceptance of plants as a suitable platform for vaccine production and in this review, we discuss the most recent advances in the production of vaccines in plants for human use.

Plant-Produced Vaccines: Future Applications in Aquaculture.

Aquaculture has undergone rapid development in the past decades. It provides a large part of high-quality protein food for humans, and thus, a sustainable aquaculture industry is of great importance for the worldwide food supply and economy. Along with the quick expansion of aquaculture, the high fish densities employed in fish farming increase the risks of outbreaks of a variety of aquatic diseases. Such diseases not only cause huge economic losses, but also lead to ecological hazards in terms of pathogen spread to marine ecosystems causing infection of wild fish and polluting the environment. Thus, fish health is essential for the aquaculture industry to be environmentally sustainable and a prerequisite for intensive aquaculture production globally. The wide use of antibiotics and drug residues has caused intensive pollution along with risks for food safety and increasing antimicrobial resistance. Vaccination is the most effective and environmentally friendly approach to battle infectious diseases in aquaculture with minimal ecological impact and is applicable to most species of farmed fish. However, there are only 34 fish vaccines commercially available globally to date, showing the urgent need for further development of fish vaccines to manage fish health and ensure food safety. Plant genetic engineering has been utilized to produce genetically modified crops with desirable characteristics and has also been used for vaccine production, with several advantages including cost-effectiveness, safety when compared with live virus vaccines, and plants being capable of carrying out posttranslational modifications that are similar to naturally occurring systems. So far, plant-derived vaccines, antibodies, and therapeutic proteins have been produced for human and animal health. However, the development of plant-made vaccines for animals, especially fish, is still lagging behind the development of human vaccines. The present review summarizes the development of fish vaccines currently utilized and the suitability of the plant-production platform for fish vaccine and then addresses considerations regarding fish vaccine production in plants. Developing fish vaccines by way of plant biotechnology are significant for the aquaculture industry, fish health management, food safety, and human health.

Bitki moleküler üretimli ilaçlar, veteriner aşılarının uygun maliyetli üretimi için umut verici bir sistemdir

Vaccination of animals has been used for centuries and is generally considered the most cost-effective and sustainable method of disease control and prevention. About twenty-five years ago, vaccines were in a inactive form or live attenuated organisms and often were not very effective. Advances in molecular biology and biotechnology have made it possible to develop new vaccines and therapeutic targes. Plant expression system has been demonstrated to be a promising platform for production of a variety of recombinant proteins such as vaccines, antibodies, therapeutic proteins, human and industrial enzymes, toxins etc. for health, agricultural and industrial applications. Although plant produced products are already available and licensed for human use, however, there are currently no plant-based vaccines on the market for animal use other than the Newcastle poultry vaccine. This is probably explained by relatively high cost of plant produced recombinant protein based vaccines for animal use. Therefore, the development of inexpensive and affordable plant-based vaccines and their formulation is very important for the production of economical animal vaccines. In this review, (1) different expression systems, (2) the history of plant-based expression systems, (3) different types of vaccines, and(4) plant-based animal vaccine production in plants are discussed. We also discussed the advantages of plants in the development of veterinary vaccines and new developed strategies that can lead to the production of cost-effective, stable and highly immunogenic veterinary vaccines.

The 5th virus-like particle and nano-particle vaccines (VLPNPV) conference

ABSTRACT Virus-like particles (VLPs) and nano-particles (NPs) are promising vaccine platforms that have led to the successful development of commercially available vaccines. The 5th international virus-like particle and nano-particle vaccines conference was held in Bern, Switzerland, from the 25th to the 27th of September in 2018. Topics included novel vaccine production techniques, methods to enhance vaccine immunogenicity, and preclinical/clinical efficacy evaluation of vaccine candidates. Here, we report on a selection of updates that were presented including the production of vaccines in plants, novel adjuvants to enhance vaccine immunogenicity, novel techniques of conjugating vaccine platforms with target antigens and the use of VLP-based vaccines for cancer and inflammatory diseases.

The 5th Congress of the Brazilian Biotechnology Society (SBBIOTEC): Meeting abstracts.

Despite Brazil's increasing production of scientific articles in the last three decades, this growth has yet to translate into an effective contribution to the economic development of this large and diverse country and to the improvement of the life standards of its population. The advances in biotechnology, whose full development relies on the elucidation of the main tenets of biology, plays an increasingly crucial role in food security, environmental remediation, sustainable bio-based industry and public health. Recognizing the key relevance of biotechnology to the overall development of our country, the Brazilian Biotechnology Society was founded in 1988. The SBBIOTEC was established to promote the overall progress of biotechnology by integrating biosciences, technology development and capacity building, aiming at contributing with positive impacts on the economic development and well-being of the Brazilian society. Scientific in its nature, from 1998 on SBBIOTEC has held Congresses in Sao Paulo, Salvador, Fortaleza and Santos. For the 5th edition of the SBBIOTEC Congress, held in the beautiful city of Florianopolis, the organizing committee thought it would generate a permanent memory of the content of the event by publishing a BMC Proceedings supplement. By capturing the current status of research and applications of biotechnology in Brazil, SBBIOTEC hopes to provide better visibility and value of the scientific contributions presented by the participants and make such an initiative an everlasting one for future Congress editions. During five days, in eight scientific sessions, an outstanding team of scientists both from public and private organizations shared their results and visions on the present and future of this fast moving area of science and technology with an audience of over 600 attendees. Some of the current advances of biotechnology research and applications in Brazil were presented together with keynote contributions from international scientists. In total, 47 oral lectures and 264 poster presentations, these last ones mostly by undergraduate and graduate students, were delivered, totaling 311 papers now available online as extended abstracts into this BMC Proceedings supplement. Presentations covered four different areas, namely: agricultural, human health, animal and industrial biotechnology. Besides the Brazilian delegates, scientists from biotech companies in Canada, USA, and Europe also came to the Congress to discuss important issues such as industrial scaling up, animal and insect gene expressions and markers for the early detection of epithelial cancer, to name a few. The program included a specific section on biofuels biotechnology, a challenging area that can be significantly boosted by metabolic and genomic engineering strategies applied to industrial yeast strains to improve bioethanol production. In human health, stem cells, tuberculosis and cancer were thoroughly discussed with emphasis on monoclonal antibodies in the therapeutic scenario. Pre-clinical and clinical trials were dealt as a critical issue to this process, particularly in light of a recent activist attack that destroyed one of the very few skilled institutions performing pre clinical trials in Brazil. In agricultural biotechnology, an area where Brazil is currently a worldwide key player, a number of important advances were presented in the area of nitrogen fixation in grasses, host pathogen interactions, and vaccine production in plants. Biological control of plant pests and human diseases such as dengue fever, and advances in RNA interference and intragenics were also hot topics of discussion. In animal husbandry the potential production of heparin in Brazil and several advances in animal gene expression were thoroughly discussed. Finally, specific sessions were devoted to the discussion of the legal framework for bioscience development, graduate training and initiatives to enhance biotechnology collaborative networks in Brazil. In closing this introductory statement, a major acknowledgement is due to the outstanding financial support provided by the Federal District Research Foundation (Fundacao de Amparo a Pesquisa do Distrito Federal FAP-DF) that made the Congress and this BMC Supplement possible. Besides the financial sponsorship of FAP-DF and an active Scientific Committee involved in abstract review, a number of people were involved in the organization and logistics. The conference would not have been possible without the valuable contributions of all these players. Given the rewarding feedback received after the Congress, we believe that the goal of providing a good mix of science and social interactions was truly accomplished, which we trust should be well illustrated by the abstracts that now follow these brief opening words.

A dual gene‐silencing vector system for monocot and dicot plants

Plant virus-based gene-silencing vectors have been extensively and successfully used to elucidate functional genomics in plants. However, only limited virus-induced gene-silencing (VIGS) vectors can be used in both monocot and dicot plants. Here, we established a dual gene-silencing vector system based on Bamboo mosaic virus (BaMV) and its satellite RNA (satBaMV). Both BaMV and satBaMV vectors could effectively silence endogenous genes in Nicotiana benthamiana and Brachypodium distachyon. The satBaMV vector could also silence the green fluorescent protein (GFP) transgene in GFP transgenic N.benthamiana. GFP transgenic plants co-agro-inoculated with BaMV and satBaMV vectors carrying sulphur and GFP genes, respectively, could simultaneously silence both genes. Moreover, the silenced plants could still survive with the silencing of genes essential for plant development such as heat-shock protein 90 (Hsp90) and Hsp70. In addition, the satBaMV- but not BaMV-based vector could enhance gene-silencing efficiency in newly emerging leaves of N.benthamiana deficient in RNA-dependant RNA polymerase 6. The dual gene-silencing vector system of BaMV and satBaMV provides a novel tool for comparative functional studies in monocot and dicot plants.

Next issue (October 2006): Plant Biotech

AbstractThis issue will deal with “green” biotechnology and covers plant genetics, breeding, agriculture and related fields. Highlights include biopharmaceutical and vaccine production in plants, the use of GFP to trace pollen movement in the field, transgene silencing in plants and much more: Read the next issue of BTJ!

Development of cowpea mosaic virus-based vectors for the production of vaccines in plants

Plant viruses are emerging as an attractive alternative to stable genetic transformation for the expression of foreign proteins in plants. The main advantages of using this strategy are that viral genomes are small and easy to manipulate, infection of plants with modified viruses is simpler and quicker than the regeneration of stably transformed plants and the sequence inserted into a virus vector will be highly amplified. One use of these virus expression systems is for vaccine production. Among plant viruses, cowpea mosaic virus makes an ideal candidate for the production of such vaccines because it grows extremely well in host plants, is very stable, and the purification of virus particles, if required, is straightforward. In this article, the authors review the progress made in the development of cowpea mosaic virus-based vectors for vaccine production, making use of two main approaches: epitope presentation and polypeptide expression.

Use of viral vectors for vaccine production in plants

The small size of plant viral genomes, the ease with which they can be manipulated, and the simplicity of the infection process is making the viral vectors an attractive alternative to the transgenic systems for the expression of foreign proteins in plants. One use of these virus expression systems is for vaccine production. There are two basic types of viral system that have been developed for the production of immunogenic peptides and proteins in plants: epitope presentation and polypeptide expression systems. In this review, we discuss advances made in this field.

Viral and host determinants of RNA virus vector replication and expression

Positive-strand RNA viruses have proven to be valuable vectors for delivery and expression of antigens for direct vaccination of animals and vaccine production in plants. However, optimal use of these viruses as vectors for vaccine and other purposes is limited by incomplete understanding of their replication pathways and associated constraints on inserted foreign genes. Further insights into RNA virus vector design and optimization are emerging from recent advances on the function of viral RNA replication factors, the nature of the viral RNA replication complex as a membrane-bounded compartment sequestering replication components from competing processes and host defenses, and identification of surprisingly diverse host genes contributing to many virus replication steps.

Research Needs to Improve Agricultural Productivity and Food Quality, with Emphasis on Biotechnology

Research into agricultural productivity, especially for crops in the developing world, should include resistance to plant viruses, fungi and the parasitic weed Striga. It must also include research into the development of resistance to Bacillus thuringiensis (Bt) toxin-expressing crops. Drought- and heat-tolerant crops, and those that can combat the problems of soil deficiencies, are required, and vaccine production in plants should be a high priority. Research into food quality should include the equivalent of "golden rice" in maize, the enhancement of the production of phytosterols and improved qualities of vegetable oils.

The potential of plant viral vectors and transgenic plants for subunit vaccine production

This chapter presents the case that plants can be used for the production of subunit vaccines and outlines the systems that are available for their production. The limits of plant biology are explored along with the limits of the differing expression systems that are available. Vaccination has led to a significant improvement in the health of the world's population. The use of vaccines has reduced the spread and infection of a number of major human diseases, including measles, mumps, rubella, and tetanus. With the advent of recombinant technologies, subunit vaccines based on proteins expressed in bacteria and yeast have grown in popularity. Because subunit vaccines do not contain an infectious agent that can revert to a more virulent form or survive the inactivation process, they offer advantages over live vaccines, because they are incapable of causing disease. Interest in vaccine production in plants has also expanded rapidly. There are considerable advantages in expressing antigenic proteins in plants. Plants can be grown locally and cheaply using standard methods, thus reducing problems with distribution, transport, and storage. Several considerations must be addressed when expressing proteins in plants for the purpose of vaccination; the protein must retain the immunogenic characteristics of the original protein and be capable of inducing a protective response to the disease.

Approaches To New Vaccines

ABSTRACT: The explosive technological advances in the fields of immunology and molecular biology in the last 5 years had an enormous impact on the identification of candidate vaccines against diseases, which until a few years ago seemed uncontrollable. Increased knowledge of the immune system has helped to define the mechanisms that underlie successful immunization and is now being exploited to develop improved versions of existing vaccines and new vaccines against emerging pathogens, tumors, or autoimmune diseases. An understanding of the mechanisms of action of novel adjuvants and the development of new vector and delivery systems will have a major impact on vaccine strategies. The use of DNA encoding antigens from pathogenic viruses, bacteria, and parasites as vaccines is a new approach that is receiving considerable attention. This and other innovative approaches, including vaccine production in plants, are appraised in this review. The successful eradication of smallpox and the imminent eradication of poliomyelitis by worldwide immunization campaigns provide positive examples of how the vaccine-mediated approach can lead to disease elimination; with the advent of new vaccines and improved delivery systems, there is no scientific reason why these successes cannot be repeated.

Production of recombinant antigens in plants for animal and human immunization - a review

Plants present a cost effective production system for high value proteins. There is an increasing world demand for cheap vaccines that can be readily administered to the population, especially in economically less developed regions. A promising concept is the production of vaccines in plants that could be grown locally. Expression of antigenic peptides in the palatable parts of plants can lead to the production of edible active vaccines. Two major strategies are: i) to express antigens in transgenic plants, and ii) to produce antigenic peptides on the surface of plant viruses that could be used to infect host plants. This review considers the experimental data and early results for both strategies, and discusses the potential and problems of this new technology