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Vaccines
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Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives
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Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccines against Tropical and other Infectious Diseases".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 12806

Special Issue Editor

Dr. Srividhya Venkataraman

E-Mail Website
Guest Editor
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada
Interests: genetic engineeering; plant-based vaccines; plant virus research; agricultural biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The development of vaccines from plants has been going on for over two decades. Vaccine production in plants requires time and a lot of effort. Researchers the world-over are involved in resolute endeavors to use all available schemes for the development of safe and efficacious vaccines against SARS-CoV-2 and other deadly viral diseases. With the introduction of transient expression technology, plant-based manufacture has been deemed as a feasible strategy which is increasingly gaining the attention of various pharmaceutical companies. Currently, few plant-produced vaccines against SARS-CoV-2 have reached the phase of preclinical and clinical trials. Nevertheless, in spite of the slow advancements in the commercialization of plant-derived vaccines, the success of clinical trials of plant-produced vaccines against influenza and COVID-19 in recent years renders great promise towards the commercialization of such plant-derived vaccines in the near future. Compared to xenobiotics, plant-based compounds are inherently safe to use due to their diminished toxicity, eco-friendliness and biocompatibility, and hence require less-rigorous appraisal. Plant-made vaccines could not be more important in tackling such unexpected pandemics as COVID-19.

The quest for efficacious plant-based biopharmaceuticals against deadly viruses such as SARS-CoV-2 is ongoing, and considering the novelty of newly emerging viruses and their variants, safety issues loom large over the use of phytochemicals and plant-based vaccines/therapeutics. This situation, combined with the dearth of information on the efficacy, quality and safety of phytochemicals, precludes their application in medical practices worldwide wherein uninvestigated usage of phytochemicals is not recommended. The marketing and well-defined use of plant-derived products must be authorized only after obtaining enough scientific data demonstrating that the pure constituent or active ingredient of the plant-based product has proven potency. The use of plant-derived vaccines is subject to stringent regulations which are, by-and-large, complex and time-consuming. The beneficial effects of plant-derived expression systems can be acquired only by circumventing regulatory hurdles.

This Special Issue aims to describe recent findings in plant-produced vaccines and the progress of plant-based vaccine candidates as well as therapeutics in pre-clinical and clinical trials. In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the recent developments in the generation of plant-based vaccines, therapeutic/drug molecules, monoclonal antibodies and phytochemicals to preclude and combat infections caused by SARS-CoV, MERS-CoV and SARS-CoV-2 viruses as well as other important viruses. 

We look forward to receiving your contributions.

Dr. Srividhya Venkataraman
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • phytochemicals
  • vaccines
  • therapeutics
  • VNPs
  • VLPs
  • Mabs
  • molecular pharming
  • viruses
  • SARS-CoV-2
  • regulatory issues

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Published Papers (5 papers)

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Research

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16 pages, 2390 KiB  
Article
Exploring the Potentiality of a Plant Platform for Monoclonal Antibody Production in Veterinary Medicine
by Bertrand Morel, Claude Favrot, Lucie Mirande, Clemens Grünwald-Gruber, Virginie Stordeur, Louis Philippe Vezina, Loïc Faye and Véronique Gomord
Vaccines 2024, 12(6), 620; https://doi.org/10.3390/vaccines12060620 - 4 Jun 2024
Viewed by 1390
Abstract
Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of [...] Read more.
Canine atopic dermatitis (CAD) is an allergic, inflammatory, and pruritic skin disease associated with the production of IgE antibodies against environmental allergens and mainly house dust mite allergens. This complex dermatological pathology involves Interleukin 31 (IL-31) as a central itch mediator. One of the most effective CAD treatments is a caninized monoclonal antibody (mAb) called Lokivetmab. It is produced in CHO cells and targets specifically canine IL-31 (cIL-31) and blocks its cellular messaging. This treatment has undoubtedly contributed to a breakthrough in dermatitis-related pruritus. However, its production in mammalian cells requires time-consuming procedures, high production costs, and investment. Plants are considered an emerging protein production platform for recombinant biopharmaceuticals due to their cost-effectiveness and rapidity for production. Here, we use transient expression in Nicotiana benthamiana plants to produce recombinant canine Interleukin 31 (cIL-31) and an anti-IL-31 monoclonal antibody (M1). First, we describe the production and characterization of M1 and then its activity on an IL-31-induced pruritic model in dogs compared to its commercial homolog. Dogs treated with the plant-made M1 mAb have shown similar improvements to Lokivetmab-treated ones after different challenges using canine IL-31. Furthermore, M1 injections were not associated with any side effects. These results demonstrate the safety and efficacy of this plant-made Lokivetmab biosimilar to control dogs’ pruritus in a well-established model. Finally, this study shows that the plant-production platform can be utilized to produce rapidly functional mAbs and bring hope to the immunotherapy field of veterinary medicine. Full article
(This article belongs to the Special Issue Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives)
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14 pages, 4121 KiB  
Article
A Monoclonal Antibody Produced in Glycoengineered Plants Potently Neutralizes Monkeypox Virus
by Adrian Esqueda, Haiyan Sun, James Bonner, Huafang Lai, Collin Jugler, Karen V. Kibler, Herta Steinkellner and Qiang Chen
Vaccines 2023, 11(7), 1179; https://doi.org/10.3390/vaccines11071179 - 30 Jun 2023
Cited by 3 | Viewed by 2256
Abstract
The 2022 global outbreaks of monkeypox virus (MPXV) and increased human-to-human transmission calls for the urgent development of countermeasures to protect people who cannot benefit from vaccination. Here, we describe the development of glycovariants of 7D11, a neutralizing monoclonal IgG antibody (mAb) directed [...] Read more.
The 2022 global outbreaks of monkeypox virus (MPXV) and increased human-to-human transmission calls for the urgent development of countermeasures to protect people who cannot benefit from vaccination. Here, we describe the development of glycovariants of 7D11, a neutralizing monoclonal IgG antibody (mAb) directed against the L1 transmembrane protein of the related vaccinia virus, in a plant-based system as a potential therapeutic against the current MPVX outbreak. Our results indicated that 7D11 mAb quickly accumulates to high levels within a week after gene introduction to plants. Plant-produced 7D11 mAb assembled correctly into the tetrameric IgG structure and can be easily purified to homogeneity. 7D11 mAb exhibited a largely homogeneous N-glycosylation profile, with or without plant-specific xylose and fucose residues, depending on the expression host, namely wild-type or glycoengineered plants. Plant-made 7D11 retained specific binding to its antigen and displayed a strong neutralization activity against MPXV, as least as potent as the reported activity against vaccinia virus. Our study highlights the utility of anti-L1 mAbs as MPXV therapeutics, and the use of glycoengineered plants to develop mAb glycovariants for potentially enhancing the efficacy of mAbs to combat ever-emerging/re-emerging viral diseases. Full article
(This article belongs to the Special Issue Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives)
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14 pages, 5197 KiB  
Article
Plant-Produced Anti-Zika Virus Monoclonal Antibody Glycovariant Exhibits Abrogated Antibody-Dependent Enhancement of Infection
by Ming Yang, Haiyan Sun, Huafang Lai, Biswas Neupane, Fengwei Bai, Herta Steinkellner and Qiang Chen
Vaccines 2023, 11(4), 755; https://doi.org/10.3390/vaccines11040755 - 29 Mar 2023
Cited by 6 | Viewed by 2336
Abstract
Monoclonal antibodies (mAb) against the envelope (E) protein of Zika virus (ZIKV) have shown great potential as therapeutics against the Zika epidemics. However, their use as a therapy may predispose treated individuals to severe infection by the related dengue virus (DENV) via antibody-dependent [...] Read more.
Monoclonal antibodies (mAb) against the envelope (E) protein of Zika virus (ZIKV) have shown great potential as therapeutics against the Zika epidemics. However, their use as a therapy may predispose treated individuals to severe infection by the related dengue virus (DENV) via antibody-dependent enhancement of infection (ADE). Here, we generated a broadly neutralizing flavivirus mAb, ZV1, with an identical protein backbone but different Fc glycosylation profiles. The three glycovariants, produced in wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants and in Chinese hamster ovary cells (ZV1WT, ZV1ΔXF, and ZV1CHO), respectively, showed equivalent neutralization potency against both ZIKV and DENV. By contrast, the three mAb glycoforms demonstrated drastically different ADE activity for DENV and ZIKV infection. While ZV1CHO and ZV1ΔXF showed ADE activity upon DENV and ZIKV infection, ZV1WT totally forwent its ADE. Importantly, all three glycovariants exhibited antibody-dependent cellular cytotoxicity (ADCC) against virus-infected cells, with increased potency by the fucose-free ZV1ΔXF glycoform. Moreover, the in vivo efficacy of the ADE-free ZV1WT was demonstrated in a murine model. Collectively, we demonstrated the feasibility of modulating ADE by Fc glycosylation, thereby establishing a novel approach for improving the safety of flavivirus therapeutics. Our study also underscores the versatile use of plants for the rapid expression of complex human proteins to reveal novel insight into antibody function and viral pathogenesis. Full article
(This article belongs to the Special Issue Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives)
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22 pages, 4061 KiB  
Article
Phytoestrogen β-Sitosterol Exhibits Potent In Vitro Antiviral Activity against Influenza A Viruses
by Sara Shokry, Akram Hegazy, Ahmad M. Abbas, Islam Mostafa, Ibrahim H. Eissa, Ahmed M. Metwaly, Galal Yahya, Assem M. El-Shazly, Khaled M. Aboshanab and Ahmed Mostafa
Vaccines 2023, 11(2), 228; https://doi.org/10.3390/vaccines11020228 - 19 Jan 2023
Cited by 14 | Viewed by 3152
Abstract
Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with [...] Read more.
Influenza is a contagious infection in humans that is caused frequently by low pathogenic seasonal influenza viruses and occasionally by pathogenic avian influenza viruses (AIV) of H5, H7, and H9 subtypes. Recently, the clinical sector in poultry and humans has been confronted with many challenges, including the limited number of antiviral drugs and the rapid evolution of drug-resistant variants. Herein, the anti-influenza activities of various plant-derived phytochemicals were investigated against highly pathogenic avian influenza A/H5N1 virus (HPAIV H5N1) and seasonal low pathogenic human influenza A/H1N1 virus (LPHIV H1N1). Out of the 22 tested phytochemicals, the steroid compounds β-sitosterol and β-sitosterol-O-glucoside have very potent activity against the predefined influenza A viruses (IAV). Both steroids could induce such activity by affecting multiple stages during IAV replication cycles, including viral adsorption and replication with a major and significant impact on the virus directly in a cell-free status “viricidal effect”. On a molecular level, several molecular docking studies suggested that β-sitosterol and β-sitosterol-O-glucoside exhibited viricidal effects through blocking active binding sites of the hemagglutinin surface protein, as well as showing inhibitory effects against replication through the binding with influenza neuraminidase activity and blocking the active sites of the M2 proton channel activity. The phytoestrogen β-sitosterol has structural similarity with the active form of the female sex hormone estradiol, and this similarity is likely one of the molecular determinants that enables the phytoestrogen β-sitosterol and its derivative to control IAV infection in vitro. This promising anti-influenza activity of β-sitosterol and its O-glycoside derivative, according to both in vitro and cheminformatics studies, recommend both phytochemicals for further studies going through preclinical and clinical phases as efficient anti-influenza drug candidates. Full article
(This article belongs to the Special Issue Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives)
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Review

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35 pages, 1985 KiB  
Review
Exigency of Plant-Based Vaccine against COVID-19 Emergence as Pandemic Preparedness
by Anirudha Chattopadhyay, A. Abdul Kader Jailani and Bikash Mandal
Vaccines 2023, 11(8), 1347; https://doi.org/10.3390/vaccines11081347 - 9 Aug 2023
Cited by 8 | Viewed by 3013
Abstract
After two years since the declaration of COVID-19 as a pandemic by the World Health Organization (WHO), more than six million deaths have occurred due to SARS-CoV-2, leading to an unprecedented disruption of the global economy. Fortunately, within a year, a wide range [...] Read more.
After two years since the declaration of COVID-19 as a pandemic by the World Health Organization (WHO), more than six million deaths have occurred due to SARS-CoV-2, leading to an unprecedented disruption of the global economy. Fortunately, within a year, a wide range of vaccines, including pathogen-based inactivated and live-attenuated vaccines, replicating and non-replicating vector-based vaccines, nucleic acid (DNA and mRNA)-based vaccines, and protein-based subunit and virus-like particle (VLP)-based vaccines, have been developed to mitigate the severe impacts of the COVID-19 pandemic. These vaccines have proven highly effective in reducing the severity of illness and preventing deaths. However, the availability and supply of COVID-19 vaccines have become an issue due to the prioritization of vaccine distribution in most countries. Additionally, as the virus continues to mutate and spread, questions have arisen regarding the effectiveness of vaccines against new strains of SARS-CoV-2 that can evade host immunity. The urgent need for booster doses to enhance immunity has been recognized. The scarcity of “safe and effective” vaccines has exacerbated global inequalities in terms of vaccine coverage. The development of COVID-19 vaccines has fallen short of the expectations set forth in 2020 and 2021. Furthermore, the equitable distribution of vaccines at the global and national levels remains a challenge, particularly in developing countries. In such circumstances, the exigency of plant virus-based vaccines has become apparent as a means to overcome supply shortages through fast manufacturing processes and to enable quick and convenient distribution to millions of people without the reliance on a cold chain system. Moreover, plant virus-based vaccines have demonstrated both safety and efficacy in eliciting robust cellular immunogenicity against COVID-19 pathogens. This review aims to shed light on the advantages and disadvantages of different types of vaccines developed against SARS-CoV-2 and provide an update on the current status of plant-based vaccines in the fight against the COVID-19 pandemic. Full article
(This article belongs to the Special Issue Plant-Produced Vaccines, Therapeutics and Phytochemicals: Recent Developments, Challenges and Perspectives)
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