Plant Based Vaccines- A Powerhouse for Global Health

A special issue of Vaccines (ISSN 2076-393X).

Deadline for manuscript submissions: closed (1 September 2021) | Viewed by 29525

Special Issue Editor


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Guest Editor
Cell and Systems Biology, University of Toronto, Toronto, ON M5S 1A1, Canada
Interests: vaccine production; biopharmaceuticals; virus replication; transgenics

Special Issue Information

Dear Colleagues,

Plants are emerging as powerful platforms for the production of biopharmaceuticals and industrial proteins. Plant-based vaccines, monoclonal antibodies and other therapeutic proteins show promise as inexpensive yet efficacious approaches to address global health. Vaccines made from plants are safe, easy to generate en masse and can be stored at ambient temperatures. These distinct properties make plant-based vaccines attractive alternatives for providing medicines which have previously been inaccessible and unaffordable to the poor in developing countries. In addition to this, plant-based vaccines can be stockpiled to guard against global pandemics such as Influenza and could been be employed in personalized medicine, such as addressing chronic diseases including cancer. Plant-based vaccines can therefore facilitate improvements in global health through multiple conduits. The following Special Issue explores various approaches used to generate plant-based vaccines, with examples provided in the context of global health

Dr. Kathleen Hefferon
Guest Editor

Manuscript Submission Information

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Keywords

  • plant made pharmaceutical
  • molecular pharming
  • agrobacterium mediated transformation
  • chloroplast
  • glycoengineering
  • monoclonal antibody
  • virus nanoparticle
  • immune response

Published Papers (7 papers)

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Research

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17 pages, 3312 KiB  
Article
Development of a SARS-CoV-2 Vaccine Candidate Using Plant-Based Manufacturing and a Tobacco Mosaic Virus-like Nano-Particle
by Joshua M. Royal, Carrie A. Simpson, Alison A. McCormick, Amanda Phillips, Steve Hume, Josh Morton, John Shepherd, Youngjun Oh, Kelsi Swope, Jennifer L. DeBeauchamp, Richard J. Webby, Robert W. Cross, Viktoriya Borisevich, Thomas W. Geisbert, Jennifer K. Demarco, Barry Bratcher, Hugh Haydon and Gregory P. Pogue
Vaccines 2021, 9(11), 1347; https://doi.org/10.3390/vaccines9111347 - 17 Nov 2021
Cited by 34 | Viewed by 5469
Abstract
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain [...] Read more.
Stable, effective, easy-to-manufacture vaccines are critical to stopping the COVID-19 pandemic resulting from the coronavirus SARS-CoV-2. We constructed a vaccine candidate CoV-RBD121-NP, which is comprised of the SARS-CoV-2 receptor-binding domain (RBD) of the spike glycoprotein (S) fused to a human IgG1 Fc domain (CoV-RBD121) and conjugated to a modified tobacco mosaic virus (TMV) nanoparticle. In vitro, CoV-RBD121 bound to the host virus receptor ACE2 and to the monoclonal antibody CR3022, a neutralizing antibody that blocks S binding to ACE2. The CoV-RBD121-NP vaccine candidate retained key SARS-CoV-2 spike protein epitopes, had consistent manufacturing release properties of safety, identity, and strength, and displayed stable potency when stored for 12 months at 2–8 °C or 22–28 °C. Immunogenicity studies revealed strong antibody responses in C57BL/6 mice with non-adjuvanted or adjuvanted (7909 CpG) formulations. The non-adjuvanted vaccine induced a balanced Th1/Th2 response and antibodies that recognized both the S1 domain and full S protein from SARS2-CoV-2, whereas the adjuvanted vaccine induced a Th1-biased response. Both adjuvanted and non-adjuvanted vaccines induced virus neutralizing titers as measured by three different assays. Collectively, these data showed the production of a stable candidate vaccine for COVID-19 through the association of the SARS-CoV-2 RBD with the TMV-like nanoparticle. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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18 pages, 4171 KiB  
Article
CoV-RBD121-NP Vaccine Candidate Protects against Symptomatic Disease following SARS-CoV-2 Challenge in K18-hACE2 Mice and Induces Protective Responses That Prevent COVID-19-Associated Immunopathology
by Jennifer K. DeMarco, Joshua M. Royal, William E. Severson, Jon D. Gabbard, Steve Hume, Josh Morton, Kelsi Swope, Carrie A. Simpson, John W. Shepherd, Barry Bratcher, Kenneth E. Palmer and Gregory P. Pogue
Vaccines 2021, 9(11), 1346; https://doi.org/10.3390/vaccines9111346 - 17 Nov 2021
Cited by 3 | Viewed by 3020
Abstract
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable [...] Read more.
We developed a SARS-CoV-2 vaccine candidate (CoV-RBD121-NP) comprised of a tobacco mosaic virus-like nanoparticle conjugated to the receptor-binding domain of the spike glycoprotein of SARS-CoV-2 fused to a human IgG1 Fc domain. CoV-RBD121-NP elicits strong antibody responses in C57BL/6 mice and is stable for up to 12 months at 2–8 or 22–28 °C. Here, we showed that this vaccine induces a strong neutralizing antibody response in K18-hACE2 mice. Furthermore, we demonstrated that immunization protects mice from virus-associated mortality and symptomatic disease. Our data indicated that a sufficient pre-existing pool of neutralizing antibodies is required to restrict SARS-CoV-2 replication upon exposure and prevent induction of inflammatory mediators associated with severe disease. Finally, we identified a potential role for CXCL5 as a protective cytokine in SARS-CoV-2 infection. Our results suggested that disruption of the CXCL5 and CXCL1/2 axis may be important early components of the inflammatory dysregulation that is characteristic of severe cases of COVID-19. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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15 pages, 4531 KiB  
Article
A Scalable Manufacturing Approach to Single Dose Vaccination against HPV
by Shuai Shao, Oscar A. Ortega-Rivera, Sayoni Ray, Jonathan K. Pokorski and Nicole F. Steinmetz
Vaccines 2021, 9(1), 66; https://doi.org/10.3390/vaccines9010066 - 19 Jan 2021
Cited by 18 | Viewed by 4984
Abstract
Human papillomavirus (HPV) is a globally prevalent sexually-transmitted pathogen, responsible for most cases of cervical cancer. HPV vaccination rates remain suboptimal, partly due to the need for multiple doses, leading to a lack of compliance and incomplete protection. To address the drawbacks of [...] Read more.
Human papillomavirus (HPV) is a globally prevalent sexually-transmitted pathogen, responsible for most cases of cervical cancer. HPV vaccination rates remain suboptimal, partly due to the need for multiple doses, leading to a lack of compliance and incomplete protection. To address the drawbacks of current HPV vaccines, we used a scalable manufacturing process to prepare implantable polymer–protein blends for single-administration with sustained delivery. Peptide epitopes from HPV16 capsid protein L2 were conjugated to the virus-like particles derived from bacteriophage Qβ, to enhance their immunogenicity. The HPV-Qβ particles were then encapsulated into poly(lactic-co-glycolic acid) (PLGA) implants, using a benchtop melt-processing system. The implants facilitated the slow and sustained release of HPV-Qβ particles without the loss of nanoparticle integrity, during high temperature melt processing. Mice vaccinated with the implants generated IgG titers comparable to the traditional soluble injections and achieved protection in a pseudovirus neutralization assay. HPV-Qβ implants offer a new vaccination platform; because the melt-processing is so versatile, the technology offers the opportunity for massive upscale into any geometric form factor. Notably, microneedle patches would allow for self-administration in the absence of a healthcare professional, within the developing world. The Qβ technology is highly adaptable, allowing the production of vaccine candidates and their delivery devices for multiple strains or types of viruses. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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13 pages, 2378 KiB  
Article
Plant-Produced Antigen Displaying Virus-Like Particles Evokes Potent Antibody Responses against West Nile Virus in Mice
by Junyun He, Huafang Lai, Adrian Esqueda and Qiang Chen
Vaccines 2021, 9(1), 60; https://doi.org/10.3390/vaccines9010060 - 17 Jan 2021
Cited by 14 | Viewed by 3162
Abstract
In this study, we developed a hepatitis B core antigen (HBcAg)-based virus-like particle (VLP) that displays the West Nile virus (WNV) Envelope protein domain III (wDIII) as a vaccine candidate for WNV. The HBcAg-wDIII fusion protein was quickly produced in Nicotiana benthamiana plants [...] Read more.
In this study, we developed a hepatitis B core antigen (HBcAg)-based virus-like particle (VLP) that displays the West Nile virus (WNV) Envelope protein domain III (wDIII) as a vaccine candidate for WNV. The HBcAg-wDIII fusion protein was quickly produced in Nicotiana benthamiana plants and reached a high expression level of approximately 1.2 mg of fusion protein per gram of leaf fresh weight within six days post gene infiltration. Electron microscopy and gradient centrifugation analysis indicated that the introduction of wDIII did not interfere with VLP formation and HBcAg-wDIII successfully assembled into VLPs. HBcAg-wDIII VLPs can be easily purified in large quantities from Nicotiana benthamiana leaves to >95% homogeneity. Further analysis revealed that the wDIII was displayed properly and demonstrated specific binding to an anti-wDIII monoclonal antibody that recognizes a conformational epitope of wDIII. Notably, HBcAg-wDIII VLPs were shown to be highly immunogenic and elicited potent humoral responses in mice with antigen-specific IgG titers equivalent to that of protective wDIII antigens in previous studies. Thus, our wDIII-based VLP vaccine offers an attractive option for developing effective, safe, and low-cost vaccines against WNV. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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15 pages, 3010 KiB  
Article
Immunogenicity of Plant-Produced Human Papillomavirus (HPV) Virus-Like Particles (VLPs)
by Paulina N. Naupu, Albertha R. van Zyl, Edward P. Rybicki and Inga I. Hitzeroth
Vaccines 2020, 8(4), 740; https://doi.org/10.3390/vaccines8040740 - 06 Dec 2020
Cited by 18 | Viewed by 3732
Abstract
Cervical cancer is ranked fourth among the top cancers in women and is the second most common cancer in low- and middle-income regions, with ~570,000 new cases reported in 2018, which attributed to 84% of worldwide cervical cancer cases. Three commercially available prophylactic [...] Read more.
Cervical cancer is ranked fourth among the top cancers in women and is the second most common cancer in low- and middle-income regions, with ~570,000 new cases reported in 2018, which attributed to 84% of worldwide cervical cancer cases. Three commercially available prophylactic Human papillomavirus (HPV) vaccines are effective at preventing HPV infections. However, these vaccines are expensive due to their complex production systems, therefore limiting their use in developing countries. Recently, the use of plants to produce vaccines has emerged as a cost-effective alternative to conventionally used expression systems. Here, L1 proteins of eight high-risk (HPV 16, 18, 31, 33, 35, 45, 52, and 58) and two low risk (HPV 6 and 34) HPV types were successfully expressed in Nicotiana benthamiana, and transmission electron microscopy (TEM) analysis showed the presence of VLPs and/or capsomeres. Immunogenicity studies were conducted in mice utilizing HPV 35, 52, and 58 and showed that type-specific L1-specific antibodies were produced which were able to successfully neutralize homologous HPV pseudovirions in pseudovirion-based neutralization assays (PBNAs). This work demonstrated the potential for using plant-based transient expression systems to produce affordable and immunogenic HPV vaccines, particularly for developing countries. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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Review

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15 pages, 3726 KiB  
Review
Frontiers in Bioengineering and Biotechnology: Plant Nanoparticles for Anti-Cancer Therapy
by Erum Shoeb, Uzma Badar, Srividhya Venkataraman and Kathleen Hefferon
Vaccines 2021, 9(8), 830; https://doi.org/10.3390/vaccines9080830 - 28 Jul 2021
Cited by 8 | Viewed by 4346
Abstract
Naturally occurring viral nanomaterials have gained popularity owing to their biocompatible and biodegradable nature. Plant virus nanoparticles (VNPs) can be used as nanocarriers for a number of biomedical applications. Plant VNPs are inexpensive to produce, safe to administer and efficacious as treatments. The [...] Read more.
Naturally occurring viral nanomaterials have gained popularity owing to their biocompatible and biodegradable nature. Plant virus nanoparticles (VNPs) can be used as nanocarriers for a number of biomedical applications. Plant VNPs are inexpensive to produce, safe to administer and efficacious as treatments. The following review describes how plant virus architecture facilitates the use of VNPs for imaging and a variety of therapeutic applications, with particular emphasis on cancer. Examples of plant viruses which have been engineered to carry drugs and diagnostic agents for specific types of cancer are provided. The drug delivery system in response to the internal conditions is known as stimuli response, recently becoming more applicable using plant viruses based VNPs. The review concludes with a perspective of the future of plant VNPs and plant virus-like particles (VLPs) in cancer research and therapy. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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18 pages, 1512 KiB  
Review
Microparticles and Nanoparticles from Plants—The Benefits of Bioencapsulation
by Jennifer Schwestka and Eva Stoger
Vaccines 2021, 9(4), 369; https://doi.org/10.3390/vaccines9040369 - 11 Apr 2021
Cited by 7 | Viewed by 3547
Abstract
The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, [...] Read more.
The efficacy of drugs and vaccines depends on their stability and ability to interact with their targets in vivo. Many drugs benefit from encapsulation, which protects them from harsh conditions and allows targeted delivery and controlled release. Although many encapsulation methods are inexpensive, such as the formulation of tablets for oral delivery, others require complex procedures that add significantly to production costs and require low-temperature transport and storage, making them inaccessible in developing countries. In this review we consider the benefits of encapsulation technologies based on plants. Plant-derived biopolymers such as starch and the maize storage protein zein are already used as protective coatings, but plant cells used as production host provide natural in vivo bioencapsulation that survives passage through the stomach and releases drugs in the intestine, due to the presence of microbes that can digest the cell wall. Proteins can also be encapsulated in subcellular compartments such as protein bodies, which ensure stability and activity while often conferring additional immunomodulatory effects. Finally, we consider the incorporation of drugs and vaccines into plant-derived nanoparticles assembled from the components of viruses. These are extremely versatile, allowing the display of epitopes and targeting peptides as well as carrying cargoes of drugs and imaging molecules. Full article
(This article belongs to the Special Issue Plant Based Vaccines- A Powerhouse for Global Health)
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