You're using an outdated browser. Please upgrade to a modern browser for the best experience.
Submitted Successfully!
Thank you for your contribution! You can also upload a video entry or images related to this topic. For video creation, please contact our Academic Video Service.
Version Summary Created by Modification Content Size Created at Operation
1 Gergana Zahmanova + 3345 word(s) 3345 2022-02-20 14:32:43 |
2 Format Change Jessie Wu Meta information modification 3345 2022-02-24 06:54:06 | |
3 Format change Jessie Wu Meta information modification 3345 2022-02-24 06:59:12 | |
4 Format Change Jessie Wu -3 word(s) 3342 2022-02-24 07:00:56 |

Video Upload Options

We provide professional Academic Video Service to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Zahmanova, G. Plant-Derived Recombinant Vaccines against Zoonotic Viruses. Encyclopedia. Available online: https://encyclopedia.pub/entry/19815 (accessed on 21 December 2025).
Zahmanova G. Plant-Derived Recombinant Vaccines against Zoonotic Viruses. Encyclopedia. Available at: https://encyclopedia.pub/entry/19815. Accessed December 21, 2025.
Zahmanova, Gergana. "Plant-Derived Recombinant Vaccines against Zoonotic Viruses" Encyclopedia, https://encyclopedia.pub/entry/19815 (accessed December 21, 2025).
Zahmanova, G. (2022, February 23). Plant-Derived Recombinant Vaccines against Zoonotic Viruses. In Encyclopedia. https://encyclopedia.pub/entry/19815
Zahmanova, Gergana. "Plant-Derived Recombinant Vaccines against Zoonotic Viruses." Encyclopedia. Web. 23 February, 2022.
Plant-Derived Recombinant Vaccines against Zoonotic Viruses
Edit
This entry is adapted from the peer-reviewed paper 10.3390/life12020156

Emerging and re-emerging zoonotic diseases cause serious illness with billions of cases, and millions of deaths. The most effective way to restrict the spread of zoonotic viruses among humans and animals and prevent disease is vaccination. Recombinant proteins produced in plants offer an alternative approach for the development of safe, effective, inexpensive candidate vaccines. Current strategies are focused on the production of highly immunogenic structural proteins, which mimic the organizations of the native virion but lack the viral genetic material. These include chimeric viral peptides, subunit virus proteins, and virus-like particles (VLPs). The latter, with their ability to self-assemble and thus resemble the form of virus particles, are gaining traction among plant-based candidate vaccines against many infectious diseases. 

zoonotic viruses plant molecular farming vaccines virus-like particles recombinant proteins

1. Introduction

Zoonoses are diseases transmitted from vertebrate animals to humans and are considered one of the most important threats to Public Health [1]. Zoonotic viruses cause illnesses with a high death rate and numerous long-term health issues. In addition, zoonotic diseases also affect the livestock sector and can have a tremendous economic impact [2]. More than 60% of emerging human infectious diseases are zoonoses and 99% of the emerging unknown viruses are zoonotic with a potentially high risk of spreading globally [3][4][5]. The recent outbreak of severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2), causing more than 5 million deaths worldwide by the end of October 2021, demonstrates the significance of zoonoses. Domestic and wild animals serve as reservoirs of zoonotic viruses, which are transmitted via direct or indirect contact [3][6][7]. The indirect transmission occurs by vectors (insects and arthropods), which significantly impacts disease transmission dynamics and complicates the measures taken to control zoonoses. Viruses, which have a transmission cycle between animal reservoirs where they primarily amplify, and their vectors (mosquitoes, ticks, midges) are known as arthropod-borne viruses or Arboviruses. Before transmission to a susceptible host, arboviruses must replicate in the arthropod vectors [8].
Vaccination is an essential method in eradicating zoonoses and the spread of highly pathogenic viruses and is of great importance to the “Global One Health” paradigm. The Global One Health Initiative’s mission includes efforts to prevent the cross-species transmission of infectious diseases, assess environmental and social impact, and develop adequate science-based risk management policies [9]. An important measure in the One Health Initiative is the creation of widely available vaccines to be used by both humans and animals. The plant expression systems may offer a successful alternative for vaccine production compared to conventional expression systems, especially for animal vaccination (Figure 1).
Life 12 00156 g001 550
Figure 1. Schematic representation of the transmission of zoonotic diseases and the used plant-based production technologies (stable, transient, and suspension cultures) for recombinant vaccine production.

2. Plants as an Expression System for Vaccine Production

For more than three decades, plants have been used for the production of therapeutic recombinant proteins, especially subunit vaccines, and VLP vaccines to cope with emerging and re-emerging diseases. Plants possess great potential in the production of vaccines because they are a safe, cost-effective, and scalable expression system. The achievements of plant molecular farming (PMF) and plant-based production of vaccines and diagnostic reagents have been summarized in a number of review articles [10][11][12][13][14][15][16]. The ability of plants to produce candidate vaccines has been demonstrated in several clinical trials, and two plant-derived vaccines (influenza vaccine and Newcastle disease vaccine) have been approved for commercial use [17][18][19]. Together with the licensing of a plant-derived recombinant human β-glucocerebrosidase, marketed as ELELYSO [20], these achievements promoted plant molecular farming and led to the rapid development of plant expression systems and the overcoming of some of their disadvantages. Increasing the yield [21], modifying plant glycosylation patterns [22], reducing the cost of production and purification [23], and increasing the recombinant protein stability [24][25][26] significantly improved the plant expression systems, making them competitive with the commercially used microbial expression systems. However, despite these achievements, the PMF has not been able to become a technology of choice for the production of pharmaceutical recombinant proteins. There are multiple and complex reasons for the slow progress of PMF. Among them are the strict regulation of GMO and pharma products. In addition, the industry is reluctant to restructure its fermentation infrastructure, and the fact that the productivity of plants, as compared to best practices, is lower also does not help the implementation of PMF in the production of recombinant protein pharmaceuticals [14]. Still, people may be witnessing a breakthrough thanks to the Medicago’s success in launching influenza and SARS-CoV-2 vaccines, which have undergone phase-3 clinical trials and are currently awaiting regulatory approval. As a result of the rapid production of large quantities of recombinant proteins within less than one week due to the transient expression approach, plant-based vaccines are becoming very attractive option when there is urgent need caused by the swift transmission of emerging pandemic viruses.
The advantages and disadvantages of the most commonly used systems for vaccine and therapeutic proteins production (Yeast, E. coli, insect cells, Chinese hamster ovary (CHO) cells, and embryonated hen’s eggs (EHE)), and their comparison with plant expression systems have been extensively reviewed by several authors [14][27][28][29]. Figure 2 summarizes the main characteristics of the used bio-pharming systems and highlights the advantages and disadvantages of plant expression systems.
Life 12 00156 g002 550
Figure 2. Comparison between plant expression systems and conventional expression systems. * N-linked glycans in humans differ from plant glycans, and the latter’s strong immunostimulatory effect may cause plant-derived therapeutics to have adverse events; however, these same properties are beneficial for vaccines as they enhance immunogenicity.
The early concept for producing cheap and easy-to-use edible vaccines, created by Charles Arntzen [30], has been studied for decades. Edible vaccines were developed, and some were used in clinical trials [31][32][33] but were later dismissed, especially for humans, mainly because of the impossibility of precise dosage of the recombinant protein within the living plant [14]. This concept of edible vaccines is still being developed for veterinary purposes [34][35][36]. Plant-made vaccines for veterinary use are very promising, mainly because of the possibility of oral delivery of the recombinant vaccine, at low cost and with a long shelf life, especially in cases where cereals are used.
Plant molecular farming is based on three main technological platforms: transient expression (generally in Nicotiana benthamiana), stable transgenic plants (transgenic and transplastomic), and plant cell-suspension cultures [37][38][39][40]. Transient expression in plants provides a higher yield of recombinant proteins within a shorter timeline than the stable modified plants and has been used successfully as a rapid response platform addressing emerging viral diseases such as Influenza and COVID 19. The production of recombinant proteins using transient expression based on RNA viral vectors has gained wide popularity due to numerous advantages: simple and easy engineering, high level of production of the protein of interest, scalability, lower risk, and lower costs [41]. Mainly small (+) RNA viruses such as tobacco mosaic virus (TMV) [42], cowpea mosaic virus (CMV) [43], and potato virus X (PVX) [40] are utilized as viral vectors for commercial protein production [44][45]. Earlier, the virus-based vectors expressed the gene of interest in addition to the virus’s own natural genes. Later on, the viruses were modified by removing all unessential elements for target protein expression, resulting in higher yield and better stability of the viral complex [46]. Transient expression, also known as agroinfiltration, involves the introduction of genes into plant leaves by infiltrating them with disarmed Agrobacterium tumefaciens carrying binary vectors [47]. The advantages of this approach have led several companies (Medicago Inc. (Québec, QC, Canada); iBio/Caliber Therapeutics (Bryan, TX, USA); Kentucky BioProcessing Inc. (KBP), Owensboro, KY, USA; Fraunhofer USA (Plymouth, MI, USA)) to invest in this plant-based platform for rapid and large-scale production of vaccines and therapeutics [48].
Stable transformation of plants takes longer, but once optimized, the transgenic system allows long-term and large-scale recombinant protein production. Various plant species such as tobacco, potato, cereals, lettuce, tomato, carrot, alfalfa, and oilseeds have been used for stable transformation by nuclear or chloroplast genome manipulation. The main approaches used to achieve stably transformed plants are Agrobacterium-mediated transformation or biolistic process [39][49]. The chloroplasts are sometimes a preferable target for stable transformation instead of the nuclei due to their high copy number in the plant cell, leading to high recombinant protein production.
The choice of technology to achieve a plant-based vaccine depends on the route of vaccine administration, the ability to achieve high levels of recombinant protein expression, and a low value of downstream processing. Edible plants (tomato, carrot, lettuce, rice, and maize) are suitable for oral administration. Cereal crops are preferable for long storage. Tobacco plants are preferable as model plants and to achieve high levels of expression.
The use of bioreactors from plant cell cultures in PMF makes it possible to overcome some of the shortcomings of transgenic crops. In vitro growing of plant cells under controlled conditions allows for the precise monitoring of cell growth and protein production and the development of good manufacturing practices. The approach of producing valuable pharmaceutical proteins in plant cell bioreactors is becoming increasingly common due to strong restrictive measures on the use of transgenic plants in the field, especially in Europe [50].

3. Virus-like Particles (VLPs) for Vaccine Development

VLPs are recognized as safe and effective vaccines against viral diseases [11][51]. They resemble regular viruses’ outer structure, composition, and size, but they lack genetic material, which makes them non-infectious [52]. Because VLPs retain the native antigenicity of the viruses they mimic, they can efficiently elicit cellular and humoral immune responses [53]. The virus-like particles can be formed from structural proteins belonging to one type or multiple types of viruses. Those composed of structural proteins or immunogenic epitopes from different viruses are known as chimeric VLPs [54][55][56][57]. Such VLPs can be used as immune modulators and self-adjuvants to provoke strong immune responses against the presented immunogenic epitopes [58][59][60]. The use of virus-like particles has also been recently utilized by the PMF community [54][61][62]. VLPs-based candidate vaccines expressed in plants have been developed against several zoonotic diseases and the efficacy of these vaccines is currently being evaluated. Chimeric plant-derived VLP vaccines are also being developed against diseases such as cancer, allergies, and autoimmune diseases [63].

4. Influenza Viruses

Influenza viruses are members of the family Orthomyxoviridae and include four genera (Influenza virus A, B, C, and D) [64]. Only influenza A and B are clinically significant for human health [65]. While influenza B infects only humans, influenza A infects humans and a wide variety of mammals and birds. The influenza A virus is zoonotic and can generate pandemic viruses by switching the host. Influenza is an enveloped virus with a spherical or pleomorphic shape, and is 80–120 nm in diameter. Its genome contains eight segments of single-stranded negative-sense RNA. The lipoprotein envelope of the influenza A virus contains two glycoproteins, hemagglutinin (HA), and neuraminidase (NA) [66]. After infection, HA and NA are the primary antigens inducing antibody production [67]. To date, 18 HA and 11 NA gene variants have been identified [68]. Of these variants, only four HA (H1, H2, H3, and H5) and two NA (N1 and N2) are considered as potentially serious pandemic threats [69]. HA is a stronger antigen than NA; thus, it is the main object of interest for vaccine development against influenza.
The World Health Organization (WHO) estimated that the flu kills about 250,000 to 500,000 people annually [70]. There is a shortage of influenza vaccines globally, and the ability for a “rapid response” vaccine production against pandemic influenza strains needs to improve [13]. Plant molecular farming technology can address these needs because it provides fast development and manufacturing of vaccines and scalable production. In 2009, the US Defense Advanced Research Projects Agency (DARPA) invested USD 100 million in four companies (Fraunhofer USA, the Center for Molecular Biotechnology in Delaware, Kentucky Bioprocessing, and Medicago Inc.) to produce 100 million influenza vaccines in plants in a month [71]. In 2012, Medicago produced 10 million doses of the H1N1 vaccine in a one-month “rapid fire test” [72]. They were able to achieve that due to many years of scientific development and the use of transient expression vectors [43], providing synthesis and accumulation of large quantities of recombinant proteins in plants within a week. D’Aoust et al. [73] demonstrated the production of VLPs composed only of influenza H5 by means of transient expression in N. benthamiana. Animal studies with low doses HA VLPs showed protective immunity in mice. The development of the candidate monovalent VLP vaccines against H5N1 pandemic strains [74][75] and the polyvalent HA VLPs for seasonal flu, which successfully passed phase-3 clinical trials [17][62][76] demonstrate the great potential plant-based technologies have in the future of vaccine production. These studies show that plant-derived HA VLPs candidate vaccines can provide protection against respiratory illnesses caused by influenza viruses in humans. Medicago Inc. has successfully completed phase-3 clinical studies for a plant-derived VLP quadrivalent flu vaccine (NCT03321968, NCT03301051, NCT03739112) [77][78]. The reported high efficacy of this plant-made flu vaccine is an important milestone in the progress of PMF.
In addition, the efficient production of hemagglutinin-based VLP vaccines in N. benthamiana has been demonstrated in academic studies by Rybicki et al. [13] and Smith et al. [79]. In Smith’s study, H6-subtype VLPs were transiently expressed and evaluated for efficacy in chickens against the heterologous H6N2 virus. Their findings demonstrate the potential of the plant-produced H6N2 HA vaccine for poultry. HA from various influenza strains was expressed in plants, and its immunogenicity was assessed [80][81][82][83][84][85][86][87][88][89]. Modifications of the HA structure were made to achieve a high level of recombinant protein accumulation: the sequences were optimized, the transmembrane domain and native signal peptide were removed, and an endoplasmic retention signal was inserted at the C terminus. The yield of the transiently expressed protein was HA variant dependent. The yield of H3 was 200 mg/kg of fresh weight (FW) tobacco leaves [81], while the yield of H1 was 400–1300 mg/kg FW [82]. Shoji et al. generated trimeric HA, which mimics the authentic HA structure, by introducing a trimerization motif from a heterologous protein into the HA sequence [83]. Immunization with the generated HA induced a protective immune response upon challenge of mice with a lethal viral dose [83]. Musiychuk et al. developed a plant expression system that achieved high-level target antigen expression in plants by engineering a thermostable carrier molecule fused to HA from the influenza A/Vietnam/04 (H5N1) virus [90].
Stable expressions of immunogens from the influenza virus are less used compared with transient expressions. In a review paper, Redkiewicz et al. summarized the results achieved from different plant expression systems for the production of HA [91]. Here, researchers will only mention some of the latest results achieved by stable expression of HA: avian H5N1 HA was found to be stably expressed in tobacco seeds [92] with a yield of 3.0 mg of the viral antigen per g of seed; and H3N2 nucleoprotein was detected in transgenic maize with a yield of 35 µg of NP/g seed [93]. The relatively low levels of recombinant protein accumulation in stable transgenic plants indicate that transient expression is more promising for developing an influenza vaccine in plants.
The feasibility of plants for the production of chimeric VLPs presenting the extracellular domain of the M2 influenza protein (M2e) as a candidate for universal influenza vaccines has also been investigated. Hepatitis B core protein (HBcAg), Hepatitis E open reading frame 2 (ORF2) capsid protein, Human papillomavirus 16 (HPV-16) L1 protein, Cowpea Mosaic Virus (CPMV), and tobacco mosaic virus (TMV) have been used as scaffolds of the M2e influenza peptide [60][94][95][96][97][98][99]. The immunogenicity of some of the chimeric VLPs presenting M2e was assessed in mice, and they often demonstrated a high immune response with protective activity [88][91][92][93]. Blokina et al. developed a chimeric protein combining the M2e and HA2 influenza A antigens with bacterial flagellin, which has adjuvant properties. The chimeric recombinant protein was expressed using a highly efficient PVX-based expression system in N. benthamiana, resulting in protein accumulation of up to 300 µg/g of fresh leaf tissue. Mice that were intranasally immunized with the purified chimeric protein survived a lethal challenge with the influenza A virus strain A/Aichi/2/68 (H3N2) [100].

5. Human immunodeficiency virus (HIV)

Human immunodeficiency virus (HIV) is classified as a member of the Lentivirus genus of the Retroviridae family [101][102]. Phylogenetical analysis showed close simian relatives of HIV-1 in chimpanzees [103] and sooty mangabeys [104], demonstrating the zoonotic origin of this virus [105]. Genetically, there are two types of HIV (HIV-1 and HIV-2). Of the two, HEV-1 has spread rapidly worldwide, and it is the primary cause of the global HIV pandemic [106].
Vaccine development against HIV is still a challenge due to the hyper-variability of the viral envelope (Env) glycoprotein, which results in immune evasion [107]. To address the global needs for HIV prevention, plants represent a viable option as a protein expression system [13][108][109].
A promising approach for an HIV vaccine is the development of artificial proteins based on conservative T-cell and B-cell epitopes. Notably, the gp41 and gp120 regions of HIV-1 are crucial to virus function and immune protection, making them valuable targets for vaccine investigation [110]. Multiple polyvalent HIV proteins have elicited immunological responses in animals. For example, the C4(V3)6 protein, based on gp120, expressed in lettuce, induced an immune response in mice [111]. The p24 protein, expressed transiently or via transplastomic or transgenic transformation, induced a humoral immune response [112][113][114]. A small epitope from gp41 displayed on the surface of CPMV stimulated an antibody response in mice [115]. HBsAg has also been utilized as a carrier for HIV polyproteins, providing excellent immunogenic characteristics while being stably expressed in N. benthamiana [116][117]. Soluble gp140 was produced and successfully co-expressed with a human chaperone protein to achieve higher yields of the viral protein [118]. gp40, produced via transient expression in N. benthamiana, formed a trimeric structure and elicited a robust immunological response in rabbits [119]. Despite the substantial number of studies on this topic, none of the HIV plant-based vaccine candidates have reached the clinical trial stages.

6. Concluding Remarks

The 21st Century has seen remarkable progress in the development of plant-based vaccines against viral diseases. Although the vast majority of these are centered on academic development and are still at the level of pre-clinical trials in animal models, people are also witnessing the significant achievements of vendors such as Medicago Inc and Kentucky Bioprocessing Inc, whose vaccine candidates against influenza and SARS-CoV-2 are likely to be licensed next year. Several factors are contributing to the observed progress in plant-based vaccine development. From a technical perspective, there is a shift from stable expression of viral proteins in transgenic plants to transient expression in N. benthamiana. The latter is much faster and can produce a decent yield of viral antigens within a week after infiltrating plant leaf material with an Agrobacterium suspension containing the target gene, offering the opportunity for a rapid response to the annual emergence of antigenically novel influenza strains or unexpected pandemics. Another very important factor for the current advancement of plant-based vaccines is the recent achievements in plant platforms that not only express target antigens but also facilitate the assembly of VLPs. The advantage of the plant-derived VLPs over simple expression of recombinant proteins in plants is that the former captures the antigenic epitopes in their native conformation, which results in enhanced immunogenicity and ultimately superior efficiency as a potential vaccine. Apart from the above-mentioned technological factors, the potential success of a Medicago plant-derived SARS-CoV-2 vaccine will accelerate the development of other plant vaccines in general.

Fischer and Buyel 2020 describe four factors that affect the selection of plant expression systems: time-to-market factors; the amount of time needed for research and development (R&D); scalability; and regulatory approval. Of the four, the time-to-market factors are the biggest determinant in the selection process. In addition, while plants offer an advantage during R&D (faster transient expression), the production upscaling of plant-produced proteins is usually a challenge. However, the approval of the new plant-based vaccines is likely to open new avenues for improved manufacturing.

The majority of the zoonotic viruses listed disproportionally affect developing countries. The development of new vaccines comes with a cost, which is a challenge for resource-limited countries that need these vaccines most. Plant-based vaccines carry the promise not only to be efficient in preventing zoonotic disease but also, importantly, to be cost-efficient and affordable.

Sustainable long-term cooperation and partnerships with global organizations (the WHO, the World Bank, and others) and governments must be established if plant molecular farming is to become a successful mainstream platform for vaccine generation and production.

References

  1. Reed, K.D. Viral Zoonoses. Ref. Module Biomed. Sci. 2018.
  2. Martins, S.B.; Häsler, B.; Rushton, J. Economic Aspects of Zoonoses: Impact of Zoonoses on the Food Industry. In Zoonoses—Infections Affecting Humans and Animals: Focus on Public Health Aspects; Sing, A., Ed.; Springer: Dordrecht, The Netherlands, 2015; pp. 1107–1126. ISBN 978-94-017-9457-2.
  3. Rahman, M.T.; Sobur, M.A.; Islam, M.S.; Ievy, S.; Hossain, M.J.; El Zowalaty, M.E.; Rahman, A.T.; Ashour, H.M. Zoonotic Diseases: Etiology, Impact, and Control. Microorganisms 2020, 8, 1405.
  4. Olival, K.J.; Hosseini, P.R.; Zambrana-Torrelio, C.; Ross, N.; Bogich, T.L.; Daszak, P. Host and Viral Traits Predict Zoonotic Spillover from Mammals. Nature 2017, 546, 646–650.
  5. Carroll, D.; Watson, B.; Togami, E.; Daszak, P.; Mazet, J.A.; Chrisman, C.J.; Rubin, E.M.; Wolfe, N.; Morel, C.M.; Gao, G.F.; et al. Building a Global Atlas of Zoonotic Viruses. Bull. World Health Organ. 2018, 96, 292–294.
  6. Belay, E.D.; Kile, J.C.; Hall, A.J.; Barton-Behravesh, C.; Parsons, M.B.; Salyer, S.J.; Walke, H. Zoonotic Disease Programs for Enhancing Global Health Security. Emerg. Infect. Dis. J. 2017, 23, S65.
  7. Rantsios, A.T. Zoonoses. Encycl. Food Health 2016, 645–653.
  8. Institute of Medicine (US) Forum on Microbial Threats. Vector-Borne Diseases: Understanding the Environmental, Human Health, and Ecological Connections, Workshop Summary; National Academies Press: Washington, DC, USA, 2008.
  9. Gebreyes, W.A.; Dupouy-Camet, J.; Newport, M.J.; Oliveira, C.J.B.; Schlesinger, L.S.; Saif, Y.M.; Kariuki, S.; Saif, L.J.; Saville, W.; Wittum, T.; et al. The Global One Health Paradigm: Challenges and Opportunities for Tackling Infectious Diseases at the Human, Animal, and Environment Interface in Low-Resource Settings. PLoS Negl. Trop. Dis. 2014, 8, e3257.
  10. Schillberg, S.; Finnern, R. Plant Molecular Farming for the Production of Valuable Proteins—Critical Evaluation of Achievements and Future Challenges. J. Plant Physiol. 2021, 258–259, 153359.
  11. Rybicki, E.P. Plant Molecular Farming of Virus-like Nanoparticles as Vaccines and Reagents. WIREs Nanomed. Nanobiotechnol. 2020, 12, e1587.
  12. Shanmugaraj, B.; Bulaon, C.J.I.; Phoolcharoen, W. Plant Molecular Farming: A Viable Platform for Recombinant Biopharmaceutical Production. Plants 2020, 9, 842.
  13. Rybicki, E.P. Plant-Based Vaccines against Viruses. Virol. J. 2014, 11, 205.
  14. Fischer, R.; Buyel, J.F. Molecular Farming—The Slope of Enlightenment. Biotechnol. Adv. 2020, 40, 107519.
  15. Gómez, M.L.; Huang, X.; Alvarez, D.; He, W.; Baysal, C.; Zhu, C.; Armario-Najera, V.; Perera, A.B.; Bennasser, P.C.; Saba-Mayoral, A.; et al. Contributions of the International Plant Science Community to the Fight against Human Infectious Diseases–Part 1: Epidemic and Pandemic Diseases. Plant Biotechnol. J. 2021, 19, 1901–1920.
  16. Ma, J.K.-C.; Drake, P.M.W.; Christou, P. The Production of Recombinant Pharmaceutical Proteins in Plants. Nat. Rev. Genet. 2003, 4, 794–805.
  17. Ward, B.J.; Makarkov, A.; Séguin, A.; Pillet, S.; Trépanier, S.; Dhaliwall, J.; Libman, M.D.; Vesikari, T.; Landry, N. Efficacy, Immunogenicity, and Safety of a Plant-Derived, Quadrivalent, Virus-like Particle Influenza Vaccine in Adults (18–64 Years) and Older Adults (≥65 Years): Two Multicentre, Randomised Phase 3 Trials. Lancet 2020, 396, 1491–1503.
  18. Vermij, P.; Waltz, E. USDA Approves the First Plant-Based Vaccine. Nat. Biotechnol. 2006, 24, 234.
  19. Lai, K.S.; Yusoff, K.; Mahmood, M. Functional Ectodomain of the Hemagglutinin-Neuraminidase Protein Is Expressed in Transgenic Tobacco Cells as a Candidate Vaccine against Newcastle Disease Virus. Plant Cell Tissue Organ Cult. 2013, 1, 117–121.
  20. Elelyso® for Gaucher Disease. Available online: https://protalix.com/about/elelyso/ (accessed on 19 November 2021).
  21. Peyret, H.; Brown, J.K.M.; Lomonossoff, G.P. Improving Plant Transient Expression through the Rational Design of Synthetic 5′ and 3′ Untranslated Regions. Plant Methods 2019, 15, 108.
  22. Montero-Morales, L.; Steinkellner, H. Advanced Plant-Based Glycan Engineering. Front. Bioeng. Biotechnol. 2018, 6, 81.
  23. Drossard, J. Downstream Processing of Plant-Derived Recombinant Therapeutic Proteins. In Molecular Farming; John Wiley & Sons: Hoboken, NJ, USA, 2004; pp. 217–231. ISBN 978-3-527-60363-3.
  24. Streatfield, S.J. Approaches to Achieve High-Level Heterologous Protein Production in Plants. Plant Biotechnol. J. 2007, 5, 2–15.
  25. Jutras, P.V.; D’Aoust, M.-A.; Couture, M.M.-J.; Vézina, L.-P.; Goulet, M.-C.; Michaud, D.; Sainsbury, F. Modulating Secretory Pathway PH by Proton Channel Co-Expression Can Increase Recombinant Protein Stability in Plants. Biotechnol. J. 2015, 10, 1478–1486.
  26. Jutras, P.V.; Dodds, I.; van der Hoorn, R.A. Proteases of Nicotiana Benthamiana: An Emerging Battle for Molecular Farming. Curr. Opin. Biotechnol. 2020, 61, 60–65.
  27. Chung, Y.H.; Church, D.; Koellhoffer, E.C.; Osota, E.; Shukla, S.; Rybicki, E.P.; Pokorski, J.K.; Steinmetz, N.F. Integrating Plant Molecular Farming and Materials Research for Next-Generation Vaccines. Nat. Rev. Mater. 2021, 1–17.
  28. LeBlanc, Z.; Waterhouse, P.; Bally, J. Plant-Based Vaccines: The Way Ahead? Viruses 2021, 13, 5.
  29. Fischer, R.; Schillberg, S. Molecular Farming: Plant-Made Pharmaceuticals and Technical Proteins; Wiley-VCH: Weinheim, Germany, 2004; ISBN 978-3-527-60363-3.
  30. Arntzen, C. Plant-Made Pharmaceuticals: From “Edible Vaccines” to Ebola Therapeutics. Plant Biotechnol. J. 2015, 13, 1013–1016.
  31. Tacket, C.O.; Mason, H.S.; Losonsky, G.; Estes, M.K.; Levine, M.M.; Arntzen, C.J. Human Immune Responses to a Novel Norwalk Virus Vaccine Delivered in Transgenic Potatoes. J. Infect. Dis. 2000, 182, 302–305.
  32. Tacket, C.O.; Mason, H.S.; Losonsky, G.; Clements, J.D.; Levine, M.M.; Arntzen, C.J. Immunogenicity in Humans of a Recombinant Bacterial Antigen Delivered in a Transgenic Potato. Nat. Med. 1998, 4, 607–609.
  33. Thanavala, Y.; Mahoney, M.; Pal, S.; Scott, A.; Richter, L.; Natarajan, N.; Goodwin, P.; Arntzen, C.J.; Mason, H.S. Immunogenicity in Humans of an Edible Vaccine for Hepatitis B. Proc. Natl. Acad. Sci. USA 2005, 102, 3378–3382.
  34. Kolotilin, I.; Topp, E.; Cox, E.; Devriendt, B.; Conrad, U.; Joensuu, J.; Stöger, E.; Warzecha, H.; McAllister, T.; Potter, A.; et al. Plant-Based Solutions for Veterinary Immunotherapeutics and Prophylactics. Vet. Res. 2014, 45, 117.
  35. Liew, P.S.; Hair-Bejo, M. Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals. Adv. Virol. 2015, 2015, 936940.
  36. Rybicki, E. History and Promise of Plant-Made Vaccines for Animals. In Prospects of Plant-Based Vaccines in Veterinary Medicine; MacDonald, J., Ed.; Springer: Cham, Switzerland, 2018; pp. 1–22. ISBN 978-3-319-90137-4.
  37. Keshavareddy, G.; Kumar, A.R.V.; Ramu, V.S. Methods of Plant Transformation—A Review. Int. J. Curr. Microbiol. Appl. Sci. 2018, 7, 2656–2668.
  38. Barampuram, S.; Zhang, Z.J. Recent Advances in Plant Transformation. Methods Mol. Biol. Clifton 2011, 701, 1–35.
  39. Krenek, P.; Samajova, O.; Luptovciak, I.; Doskocilova, A.; Komis, G.; Samaj, J. Transient Plant Transformation Mediated by Agrobacterium Tumefaciens: Principles, Methods and Applications. Biotechnol. Adv. 2015, 33, 1024–1042.
  40. Mardanova, E.S.; Blokhina, E.A.; Tsybalova, L.M.; Peyret, H.; Lomonossoff, G.P.; Ravin, N.V. Efficient Transient Expression of Recombinant Proteins in Plants by the Novel PEff Vector Based on the Genome of Potato Virus X. Front. Plant Sci. 2017, 8, 247.
  41. Naseri, Z.; Khezri, G.; Davarpanah, S.J.; Ofoghi, H. Virus-Based Vectors: A New Approach for Production of Recombinant Proteins. J. Appl. Biotechnol. Rep. 2019, 6, 6–14.
  42. Gleba, Y.; Klimyuk, V.; Marillonnet, S. Viral Vectors for the Expression of Proteins in Plants. Curr. Opin. Biotechnol. 2007, 18, 134–141.
  43. Sainsbury, F.; Thuenemann, E.C.; Lomonossoff, G.P. PEAQ: Versatile Expression Vectors for Easy and Quick Transient Expression of Heterologous Proteins in Plants. Plant Biotechnol. J. 2009, 7, 682–693.
  44. Venkataraman, S.; Hefferon, K. Application of Plant Viruses in Biotechnology, Medicine, and Human Health. Viruses 2021, 13, 1697.
  45. Peyret, H.; Lomonossoff, G.P. When Plant Virology Met Agrobacterium: The Rise of the Deconstructed Clones. Plant Biotechnol. J. 2015, 13, 1121–1135.
  46. Sainsbury, F. Innovation in Plant-Based Transient Protein Expression for Infectious Disease Prevention and Preparedness. Curr. Opin. Biotechnol. 2020, 61, 110–115.
  47. Bally, J.; Jung, H.; Mortimer, C.; Naim, F.; Philips, J.G.; Hellens, R.; Bombarely, A.; Goodin, M.M.; Waterhouse, P.M. The Rise and Rise of Nicotiana Benthamiana: A Plant for All Reasons. Annu. Rev. Phytopathol. 2018, 56, 405–426.
  48. Shahid, N.; Daniell, H. Plant-Based Oral Vaccines against Zoonotic and Non-Zoonotic Diseases. Plant Biotechnol. J. 2016, 14, 2079–2099.
  49. Twyman, R.M.; Christou, P. Plant Transformation Technology: Particle Bombardment. In Handbook of Plant Biotechnology; John Wiley & Sons: Hoboken, NJ, USA, 2004; ISBN 978-0-470-86914-7.
  50. Xu, J.; Zhang, N. On the Way to Commercializing Plant Cell Culture Platform for Biopharmaceuticals: Present Status and Prospect. Pharm. Bioprocess. 2014, 2, 499–518.
  51. Marsian, J.; Lomonossoff, G.P. Molecular Pharming—VLPs Made in Plants. Curr. Opin. Biotechnol. 2016, 37, 201–206.
  52. Zeltins, A. Protein Complexes and Virus-Like Particle Technology. Subcell. Biochem. 2018, 88, 379–405.
  53. Wang, C.; Zheng, X.; Gai, W.; Wong, G.; Wang, H.; Jin, H.; Feng, N.; Zhao, Y.; Zhang, W.; Li, N.; et al. Novel Chimeric Virus-like Particles Vaccine Displaying MERS-CoV Receptor-Binding Domain Induce Specific Humoral and Cellular Immune Response in Mice. Antivir. Res. 2017, 140, 55–61.
  54. Chen, Q.; Lai, H. Plant-Derived Virus-like Particles as Vaccines. Hum. Vaccines Immunother. 2013, 9, 26–49.
  55. Rutkowska, D.A.; Mokoena, N.B.; Tsekoa, T.L.; Dibakwane, V.S.; O’Kennedy, M.M. Plant-Produced Chimeric Virus-like Particles—A New Generation Vaccine against African Horse Sickness. BMC Vet. Res. 2019, 15, 432.
  56. Zahmanova, G.; Mazalovska, M.; Takova, K.; Toneva, V.; Minkov, I.; Peyret, H.; Lomonossoff, G. Efficient Production of Chimeric Hepatitis B Virus-Like Particles Bearing an Epitope of Hepatitis E Virus Capsid by Transient Expression in Nicotiana Benthamiana. Life 2021, 11, 64.
  57. Nooraei, S.; Bahrulolum, H.; Hoseini, Z.S.; Katalani, C.; Hajizade, A.; Easton, A.J.; Ahmadian, G. Virus-like Particles: Preparation, Immunogenicity and Their Roles as Nanovaccines and Drug Nanocarriers. J. Nanobiotechnol. 2021, 19, 59.
  58. Lomonossoff, G.P. Virus Particles and the Uses of Such Particles in Bio- and Nanotechnology. In Recent Advances in Plant Virology; Caister Academic Press: Poole, UK, 2011.
  59. Mardanova, E.S.; Kotlyarov, R.Y.; Kuprianov, V.V.; Stepanova, L.A.; Tsybalova, L.M.; Lomonosoff, G.P.; Ravin, N.V. Rapid High-Yield Expression of a Candidate Influenza Vaccine Based on the Ectodomain of M2 Protein Linked to Flagellin in Plants Using Viral Vectors. BMC Biotechnol. 2015, 15, 42.
  60. Matić, S.; Rinaldi, R.; Masenga, V.; Noris, E. Efficient Production of Chimeric Human Papillomavirus 16 L1 Protein Bearing the M2e Influenza Epitope in Nicotiana Benthamiana Plants. BMC Biotechnol. 2011, 11, 106.
  61. Medicago Inc. Plant-Derived Vaccines. Biopharma Dealmakers (Biopharm Deal). 2018. Available online: https://www.nature.com/articles/d43747-020-00537-y (accessed on 19 November 2021).
  62. Pillet, S.; Aubin, É.; Trépanier, S.; Bussière, D.; Dargis, M.; Poulin, J.-F.; Yassine-Diab, B.; Ward, B.J.; Landry, N. A Plant-Derived Quadrivalent Virus like Particle Influenza Vaccine Induces Cross-Reactive Antibody and T Cell Response in Healthy Adults. Clin. Immunol. 2016, 168, 72–87.
  63. Balke, I.; Zeltins, A. Recent Advances in the Use of Plant Virus-Like Particles as Vaccines. Viruses 2020, 12, 270.
  64. Lefkowitz, E.J.; Dempsey, D.M.; Hendrickson, R.C.; Orton, R.J.; Siddell, S.G.; Smith, D.B. Virus Taxonomy: The Database of the International Committee on Taxonomy of Viruses (ICTV). Nucleic Acids Res. 2018, 46, D708–D717.
  65. Hay, A.J.; Gregory, V.; Douglas, A.R.; Lin, Y.P. The Evolution of Human Influenza Viruses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2001, 356, 1861–1870.
  66. Cox, N.J.; Subbarao, K. Global Epidemiology of Influenza: Past and Present. Annu. Rev. Med. 2000, 51, 407–421.
  67. Krammer, F. The Human Antibody Response to Influenza A Virus Infection and Vaccination. Nat. Rev. Immunol. 2019, 19, 383–397.
  68. Shao, W.; Li, X.; Goraya, M.U.; Wang, S.; Chen, J.-L. Evolution of Influenza A Virus by Mutation and Re-Assortment. Int. J. Mol. Sci. 2017, 18, 1650.
  69. Proença-Módena, J.L.; Macedo, I.S.; Arruda, E. H5N1 Avian Influenza Virus: An Overview. Braz. J. Infect. Dis. 2007, 11, 125–133.
  70. Paget, J.; Spreeuwenberg, P.; Charu, V.; Taylor, R.J.; Iuliano, A.D.; Bresee, J.; Simonsen, L.; Viboud, C. Global Seasonal Influenza-associated Mortality Collaborator Network and GLaMOR Collaborating Teams* Global Mortality Associated with Seasonal Influenza Epidemics: New Burden Estimates and Predictors from the GLaMOR Project. J. Glob. Health 2019, 9, 020421.
  71. Pellerin, C. DARPA Effort Speeds Bio-Threat Response. Available online: https://www.army.mil/article/47617/darpa_effort_speeds_bio_threat_response (accessed on 19 November 2021).
  72. Medicago Inc. Final Short Form Prospectus. Available online: https://sec.report/otc/financial-report/93315 (accessed on 19 November 2021).
  73. D’Aoust, M.-A.; Lavoie, P.-O.; Couture, M.M.-J.; Trépanier, S.; Guay, J.-M.; Dargis, M.; Mongrand, S.; Landry, N.; Ward, B.J.; Vézina, L.-P. Influenza Virus-like Particles Produced by Transient Expression in Nicotiana Benthamiana Induce a Protective Immune Response against a Lethal Viral Challenge in Mice. Plant Biotechnol. J. 2008, 6, 930–940.
  74. Landry, N.; Ward, B.J.; Trépanier, S.; Montomoli, E.; Dargis, M.; Lapini, G.; Vézina, L.-P. Preclinical and Clinical Development of Plant-Made Virus-Like Particle Vaccine against Avian H5N1 Influenza. PLoS ONE 2010, 5, e15559.
  75. Pillet, S.; Aubin, É.; Trépanier, S.; Poulin, J.-F.; Yassine-Diab, B.; ter Meulen, J.; Ward, B.J.; Landry, N. Humoral and Cell-Mediated Immune Responses to H5N1 Plant-Made Virus-like Particle Vaccine Are Differentially Impacted by Alum and GLA-SE Adjuvants in a Phase 2 Clinical Trial. npj Vaccines 2018, 3, 3.
  76. Pillet, S.; Couillard, J.; Trépanier, S.; Poulin, J.-F.; Yassine-Diab, B.; Guy, B.; Ward, B.J.; Landry, N. Immunogenicity and Safety of a Quadrivalent Plant-Derived Virus like Particle Influenza Vaccine Candidate—Two Randomized Phase II Clinical Trials in 18 to 49 and ≥50 Years Old Adults. PLoS ONE 2019, 14, e0216533.
  77. Tripathy, S.; Dassarma, B.; Bhattacharya, M.; Matsabisa, M.G. Plant-Based Vaccine Research Development against Viral Diseases with Emphasis on Ebola Virus Disease: A Review Study. Curr. Opin. Pharmacol. 2021, 60, 261–267.
  78. Home—ClinicalTrials.Gov. Available online: https://www.clinicaltrials.gov/ (accessed on 19 November 2021).
  79. Smith, T.; O’Kennedy, M.M.; Wandrag, D.B.R.; Adeyemi, M.; Abolnik, C. Efficacy of a Plant-Produced Virus-like Particle Vaccine in Chickens Challenged with Influenza A H6N2 Virus. Plant Biotechnol. J. 2020, 18, 502–512.
  80. Shoji, Y.; Bi, H.; Musiychuk, K.; Rhee, A.; Horsey, A.; Roy, G.; Green, B.; Shamloul, M.; Farrance, C.E.; Taggart, B.; et al. Plant-Derived Hemagglutinin Protects Ferrets against Challenge Infection with the A/Indonesia/05/05 Strain of Avian Influenza. Vaccine 2009, 27, 1087–1092.
  81. Shoji, Y.; Chichester, J.A.; Bi, H.; Musiychuk, K.; de la Rosa, P.; Goldschmidt, L.; Horsey, A.; Ugulava, N.; Palmer, G.A.; Mett, V.; et al. Plant-Expressed HA as a Seasonal Influenza Vaccine Candidate. Vaccine 2008, 26, 2930–2934.
  82. Shoji, Y.; Farrance, C.E.; Bautista, J.; Bi, H.; Musiychuk, K.; Horsey, A.; Park, H.; Jaje, J.; Green, B.J.; Shamloul, M.; et al. A Plant-Based System for Rapid Production of Influenza Vaccine Antigens. Influenza Other Respir. Viruses 2012, 6, 204–210.
  83. Shoji, Y.; Jones, R.M.; Mett, V.; Chichester, J.A.; Musiychuk, K.; Sun, X.; Tumpey, T.M.; Green, B.J.; Shamloul, M.; Norikane, J.; et al. A Plant-Produced H1N1 Trimeric Hemagglutinin Protects Mice from a Lethal Influenza Virus Challenge. Hum. Vaccines Immunother. 2013, 9, 553–560.
  84. Phan, H.T.; Pham, V.T.; Ho, T.T.; Pham, N.B.; Chu, H.H.; Vu, T.H.; Abdelwhab, E.M.; Scheibner, D.; Mettenleiter, T.C.; Hanh, T.X.; et al. Immunization with Plant-Derived Multimeric H5 Hemagglutinins Protect Chicken against Highly Pathogenic Avian Influenza Virus H5N1. Vaccines 2020, 8, 593.
  85. Phan, H.T.; Ho, T.T.; Chu, H.H.; Vu, T.H.; Gresch, U.; Conrad, U. Neutralizing Immune Responses Induced by Oligomeric H5N1-Hemagglutinins from Plants. Vet. Res. 2017, 48, 53.
  86. Phan, H.T.; Hause, B.; Hause, G.; Arcalis, E.; Stoger, E.; Maresch, D.; Altmann, F.; Joensuu, J.; Conrad, U. Influence of Elastin-Like Polypeptide and Hydrophobin on Recombinant Hemagglutinin Accumulations in Transgenic Tobacco Plants. PLoS ONE 2014, 9, e99347.
  87. Phan, H.T.; Gresch, U.; Conrad, U. In Vitro-Formulated Oligomers of Strep-Tagged Avian Influenza Haemagglutinin Produced in Plants Cause Neutralizing Immune Responses. Front. Bioeng. Biotechnol. 2018, 6, 115.
  88. Phan, H.T.; Pohl, J.; Floss, D.M.; Rabenstein, F.; Veits, J.; Le, B.T.; Chu, H.H.; Hause, G.; Mettenleiter, T.; Conrad, U. ELPylated Haemagglutinins Produced in Tobacco Plants Induce Potentially Neutralizing Antibodies against H5N1 Viruses in Mice. Plant Biotechnol. J. 2013, 11, 582–593.
  89. Mett, V.; Musiychuk, K.; Bi, H.; Farrance, C.E.; Horsey, A.; Ugulava, N.; Shoji, Y.; de la Rosa, P.; Palmer, G.A.; Rabindran, S.; et al. A Plant-Produced Influenza Subunit Vaccine Protects Ferrets against Virus Challenge. Influenza Other Respir. Viruses 2008, 2, 33–40.
  90. Musiychuk, K.; Stephenson, N.; Bi, H.; Farrance, C.E.; Orozovic, G.; Brodelius, M.; Brodelius, P.; Horsey, A.; Ugulava, N.; Shamloul, A.-M.; et al. A Launch Vector for the Production of Vaccine Antigens in Plants. Influenza Other Respir. Viruses 2007, 1, 19–25.
  91. Redkiewicz, P.; Sirko, A.; Kamel, K.A.; Góra-Sochacka, A. Plant Expression Systems for Production of Hemagglutinin as a Vaccine against Influenza Virus. Acta Biochim. Pol. 2014, 61, 551–560.
  92. Ceballo, Y.; Tiel, K.; López, A.; Cabrera, G.; Pérez, M.; Ramos, O.; Rosabal, Y.; Montero, C.; Menassa, R.; Depicker, A.; et al. High Accumulation in Tobacco Seeds of Hemagglutinin Antigen from Avian (H5N1) Influenza. Transgenic Res. 2017, 26, 775–789.
  93. Nahampun, H.N.; Bosworth, B.; Cunnick, J.; Mogler, M.; Wang, K. Expression of H3N2 Nucleoprotein in Maize Seeds and Immunogenicity in Mice. Plant Cell Rep. 2015, 34, 969–980.
  94. Thuenemann, E.C.; Lenzi, P.; Love, A.J.; Taliansky, M.; Bécares, M.; Zuñiga, S.; Enjuanes, L.; Zahmanova, G.G.; Minkov, I.N.; Matić, S.; et al. The Use of Transient Expression Systems for the Rapid Production of Virus-like Particles in Plants. Curr. Pharm. Des. 2013, 19, 5564–5573.
  95. Zahmanova, G.G.; Mazalovska, M.; Takova, K.H.; Toneva, V.T.; Minkov, I.N.; Mardanova, E.S.; Ravin, N.V.; Lomonossoff, G.P. Rapid High-Yield Transient Expression of Swine Hepatitis E ORF2 Capsid Proteins in Nicotiana Benthamiana Plants and Production of Chimeric Hepatitis E Virus-Like Particles Bearing the M2e Influenza Epitope. Plants 2019, 9, 29.
  96. Meshcheryakova, Y.A.; Eldarov, M.A.; Migunov, A.I.; Stepanova, L.A.; Repko, I.A.; Kiselev, C.I.; Lomonossoff, G.P.; Skryabin, K.G. Cowpea Mosaic Virus Chimeric Particles Bearing the Ectodomain of Matrix Protein 2 (M2E) of the Influenza a Virus: Production and Characterization. Mol. Biol. 2009, 43, 685–694.
  97. Petukhova, N.V.; Gasanova, T.V.; Ivanov, P.A.; Atabekov, J.G. High-Level Systemic Expression of Conserved Influenza Epitope in Plants on the Surface of Rod-Shaped Chimeric Particles. Viruses 2014, 6, 1789–1800.
  98. Ravin, N.V.; Kotlyarov, R.Y.; Mardanova, E.S.; Kuprianov, V.V.; Migunov, A.I.; Stepanova, L.A.; Tsybalova, L.M.; Kiselev, O.I.; Skryabin, K.G. Plant-Produced Recombinant Influenza Vaccine Based on Virus-like HBc Particles Carrying an Extracellular Domain of M2 Protein. Biochem. Mosc. 2012, 77, 33–40.
  99. Petukhova, N.V.; Gasanova, T.V.; Stepanova, L.A.; Rusova, O.A.; Potapchuk, M.V.; Korotkov, A.V.; Skurat, E.V.; Tsybalova, L.M.; Kiselev, O.I.; Ivanov, P.A.; et al. Immunogenicity and Protective Efficacy of Candidate Universal Influenza A Nanovaccines Produced in Plants by Tobacco Mosaic Virus-Based Vectors. Curr. Pharm. Des. 2013, 19, 5587–5600.
  100. Blokhina, E.A.; Mardanova, E.S.; Stepanova, L.A.; Tsybalova, L.M.; Ravin, N.V. Plant-Produced Recombinant Influenza A Virus Candidate Vaccine Based on Flagellin Linked to Conservative Fragments of M2 Protein and Hemagglutintin. Plants 2020, 9, 162.
  101. Barré-Sinoussi, F.; Chermann, J.C.; Rey, F.; Nugeyre, M.T.; Chamaret, S.; Gruest, J.; Dauguet, C.; Axler-Blin, C.; Vézinet-Brun, F.; Rouzioux, C.; et al. Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS). Science 1983, 220, 868–871.
  102. Gallo, R.C.; Salahuddin, S.Z.; Popovic, M.; Shearer, G.M.; Kaplan, M.; Haynes, B.F.; Palker, T.J.; Redfield, R.; Oleske, J.; Safai, B. Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDS. Science 1984, 224, 500–503.
  103. Huet, T.; Cheynier, R.; Meyerhans, A.; Roelants, G.; Wain-Hobson, S. Genetic Organization of a Chimpanzee Lentivirus Related to HIV-1. Nature 1990, 345, 356–359.
  104. Hirsch, V.M.; Olmsted, R.A.; Murphey-Corb, M.; Purcell, R.H.; Johnson, P.R. An African Primate Lentivirus SIVsmclosely Related to HIV-2. Nature 1989, 339, 389–392.
  105. Sharp, P.M.; Hahn, B.H. Origins of HIV and the AIDS Pandemic. Cold Spring Harb. Perspect. Med. 2011, 1, a006841.
  106. De Cock, K.M.; Adjorlolo, G.; Ekpini, E.; Sibailly, T.; Kouadio, J.; Maran, M.; Brattegaard, K.; Vetter, K.M.; Doorly, R.; Gayle, H.D. Epidemiology and Transmission of HIV-2: Why There Is No HIV-2 Pandemic. JAMA 1993, 270, 2083–2086.
  107. van Schooten, J.; van Gils, M.J. HIV-1 Immunogens and Strategies to Drive Antibody Responses towards Neutralization Breadth. Retrovirology 2018, 15, 74.
  108. Tremouillaux-Guiller, J.; Moustafa, K.; Hefferon, K.; Gaobotse, G.; Makhzoum, A. Plant-Made HIV Vaccines and Potential Candidates. Curr. Opin. Biotechnol. 2020, 61, 209–216.
  109. Scotti, N.; Buonaguro, L.; Tornesello, M.L.; Cardi, T.; Buonaguro, F.M. Plant-Based Anti-HIV-1 Strategies: Vaccine Molecules and Antiviral Approaches. Expert Rev. Vaccines 2010, 9, 925–936.
  110. Zolla-Pazner, S. Identifying Epitopes of HIV-1 That Induce Protective Antibodies. Nat. Rev. Immunol. 2004, 4, 199–210.
  111. Govea-Alonso, D.O.; Gómez-Cardona, E.E.; Rubio-Infante, N.; García-Hernández, A.L.; Varona-Santos, J.T.; Salgado-Bustamante, M.; Korban, S.S.; Moreno-Fierros, L.; Rosales-Mendoza, S. Production of an Antigenic C4(V3)6 Multiepitopic HIV Protein in Bacterial and Plant Systems. Plant Cell Tissue Organ Cult. 2013, 113, 73–79.
  112. Lindh, I.; Kalbina, I.; Thulin, S.; Scherbak, N.; Sävenstrand, H.; Bråve, A.; Hinkula, J.; Strid, Å.; Andersson, S. Feeding of Mice with Arabidopsis Thaliana Expressing the HIV-1 Subtype C P24 Antigen Gives Rise to Systemic Immune Responses. APMIS 2008, 116, 985–994.
  113. Gonzalez-Rabade, N.; McGowan, E.G.; Zhou, F.; McCabe, M.S.; Bock, R.; Dix, P.J.; Gray, J.C.; Ma, J.K.-C. Immunogenicity of Chloroplast-Derived HIV-1 P24 and a P24-Nef Fusion Protein Following Subcutaneous and Oral Administration in Mice. Plant Biotechnol. J. 2011, 9, 629–638.
  114. Pérez-Filgueira, D.M.; Brayfield, B.P.; Phiri, S.; Borca, M.V.; Wood, C.; Morris, T.J. Preserved Antigenicity of HIV-1 P24 Produced and Purified in High Yields from Plants Inoculated with a Tobacco Mosaic Virus (TMV)-Derived Vector. J. Virol. Methods 2004, 121, 201–208.
  115. McLain, L.; Durrani, Z.; Wisniewski, L.A.; Porta, C.; Lomonossoff, G.P.; Dimmock, N.J. Stimulation of Neutralizing Antibodies to Human Immunodeficiency Virus Type 1 in Three Strains of Mice Immunized with a 22 Amino Acid Peptide of Gp41 Expressed on the Surface of a Plant Virus. Vaccine 1996, 14, 799–810.
  116. Guetard, D.; Greco, R.; Cervantes Gonzalez, M.; Celli, S.; Kostrzak, A.; Langlade-Demoyen, P.; Sala, F.; Wain-Hobson, S.; Sala, M. Immunogenicity and Tolerance Following HIV-1/HBV Plant-Based Oral Vaccine Administration. Vaccine 2008, 26, 4477–4485.
  117. Greco, R.; Michel, M.; Guetard, D.; Cervantes-Gonzalez, M.; Pelucchi, N.; Wain-Hobson, S.; Sala, F.; Sala, M. Production of Recombinant HIV-1/HBV Virus-like Particles in Nicotiana Tabacum and Arabidopsis Thaliana Plants for a Bivalent Plant-Based Vaccine. Vaccine 2007, 25, 8228–8240.
  118. Margolin, E.; Oh, Y.J.; Verbeek, M.; Naude, J.; Ponndorf, D.; Meshcheriakova, Y.A.; Peyret, H.; van Diepen, M.T.; Chapman, R.; Meyers, A.E.; et al. Co-expression of Human Calreticulin Significantly Improves the Production of HIV Gp140 and Other Viral Glycoproteins in Plants. Plant Biotechnol. J. 2020, 18, 2109–2117.
  119. Margolin, E.; Chapman, R.; Meyers, A.E.; van Diepen, M.T.; Ximba, P.; Hermanus, T.; Crowther, C.; Weber, B.; Morris, L.; Williamson, A.-L.; et al. Production and Immunogenicity of Soluble Plant-Produced HIV-1 Subtype C Envelope Gp140 Immunogens. Front. Plant Sci. 2019, 10, 1378.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Biotechnology & Applied Microbiology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : Gergana Zahmanova
View Times: 1.0K
Revisions: 4 times (View History)
Update Date: 24 Feb 2022
Table of Contents
    Notice
    You are not a member of the advisory board for this topic. If you want to update advisory board member profile, please contact office@encyclopedia.pub.
    OK
    Confirm
    Only members of the Encyclopedia advisory board for this topic are allowed to note entries. Would you like to become an advisory board member of the Encyclopedia?
    Yes
    No
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    There is no comment~
    ${ textCharacter }/${ maxCharacter }
    Submit
    Cancel
    ${ selectedItem.replyTextCharacter }/${ selectedItem.replyMaxCharacter }
    Submit
    Cancel
    Confirm
    Are you sure to Delete?
    Yes No
    Academic Video Service
    Feedback