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11 pages, 1443 KiB

Open AccessArticle

Antibody-Dependent Enhancement Activity of a Plant-Made Vaccine against West Nile Virus

by Haiyan Sun, Dhiraj Acharya, Amber M. Paul, Huafang Lai, Junyun He, Fengwei Bai and Qiang Chen

Vaccines 2023, 11(2), 197; https://doi.org/10.3390/vaccines11020197 - 17 Jan 2023

Cited by 10 | Viewed by 2864

Abstract

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major [...] Read more.

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue (DENV) virus. Specifically, a plant-produced virus-like particle (VLP) that displays the WNV Envelope protein domain III (wDIII) elicited both high neutralizing antibody titers and antigen-specific cellular immune responses in mice. Passive transfer of serum from VLP-vaccinated mice protected recipient mice from a lethal challenge of WNV infection. Notably, VLP-induced antibodies did not enhance the infection of Fc gamma receptor-expressing K562 cells by ZIKV or DENV through ADE. Thus, a plant-made wDIII-displaying VLP presents a promising WNV vaccine candidate that induces protective immunity and minimizes the concern of inducing ADE-prone antibodies to predispose vaccinees to severe infection by DENV or ZIKV. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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15 pages, 1663 KiB

Open AccessArticle

Potential for a Plant-Made SARS-CoV-2 Neutralizing Monoclonal Antibody as a Synergetic Cocktail Component

by Collin Jugler, Haiyan Sun, Francisca Grill, Karen Kibler, Adrian Esqueda, Huafang Lai, Yize Li, Douglas Lake and Qiang Chen

Vaccines 2022, 10(5), 772; https://doi.org/10.3390/vaccines10050772 - 12 May 2022

Cited by 10 | Viewed by 4449

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a public health crisis over the last two years. Monoclonal antibody (mAb)-based therapeutics against the spike (S) protein have been shown to be effective treatments for SARS-CoV-2 infection, especially the original viral strain. However, the current mAbs produced in mammalian cells are expensive and might be unaffordable for many. Furthermore, the emergence of variants of concern demands the development of strategies to prevent mutant escape from mAb treatment. Using a cocktail of mAbs that bind to complementary neutralizing epitopes is one such strategy. In this study, we use Nicotiana benthamiana plants in an effort to expedite the development of efficacious and affordable antibody cocktails against SARS-CoV-2. We show that two mAbs can be highly expressed in plants and are correctly assembled into IgG molecules. Moreover, they retain target epitope recognition and, more importantly, neutralize multiple SARS-CoV-2 variants. We also show that one plant-made mAb has neutralizing synergy with other mAbs that we developed in hybridomas. This is the first report of a plant-made mAb to be assessed as a potential component of a SARS-CoV-2 neutralizing cocktail. This work may offer a strategy for using plants to quickly develop mAb cocktail-based therapeutics against emerging viral diseases with high efficacy and low costs. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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12 pages, 1457 KiB

Open AccessArticle

SARS-CoV-2 Spike Protein-Induced Interleukin 6 Signaling Is Blocked by a Plant-Produced Anti-Interleukin 6 Receptor Monoclonal Antibody

by Collin Jugler, Haiyan Sun and Qiang Chen

Vaccines 2021, 9(11), 1365; https://doi.org/10.3390/vaccines9111365 - 20 Nov 2021

Cited by 16 | Viewed by 5215

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute [...] Read more.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the current COVID-19 pandemic, has caused more than 4.5 million deaths worldwide. Severe and fatal cases of COVID-19 are often associated with increased proinflammatory cytokine levels including interleukin 6 (IL-6) and acute respiratory distress syndrome. In this study, we explored the feasibility of using plants to produce an anti-IL-6 receptor (IL-6R) monoclonal antibody (mAb) and examined its utility in reducing IL-6 signaling in an in vitro model, which simulates IL-6 induction during SARS-CoV-2 infection. The anti-IL6R mAb (IL6RmAb) was quickly expressed and correctly assembled in Nicotiana benthamiana leaves. Plant-produced IL6RmAb (pIL6RmAb) could be enriched to homogeneity by a simple purification scheme. Furthermore, pIL6RmAb was shown to effectively inhibit IL-6 signaling in a cell-based model system. Notably, pIL6RmAb also suppressed IL-6 signaling that was induced by the exposure of human peripheral blood mononuclear cells to the spike protein of SARS-CoV-2. This is the first report of a plant-made anti-IL-6R mAb and its activity against SARS-CoV-2-related cytokine signaling. This study demonstrates the capacity of plants for producing functionally active mAbs that block cytokine signaling and implies their potential efficacy to curb cytokine storm in COVID-19 patients. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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13 pages, 1718 KiB

Open AccessArticle

Development and Optimization of an Enzyme Immunoassay to Detect Serum Antibodies against the Hepatitis E Virus in Pigs, Using Plant-Derived ORF2 Recombinant Protein

by Katerina Takova, Tsvetoslav Koynarski, George Minkov, Valentina Toneva, Eugenia Mardanova, Nikolai Ravin, Georgi L. Lukov and Gergana Zahmanova

Vaccines 2021, 9(9), 991; https://doi.org/10.3390/vaccines9090991 - 6 Sep 2021

Cited by 11 | Viewed by 4376

Abstract

Hepatitis E is an emerging global disease, mainly transmitted via the fecal–oral route in developing countries, and in a zoonotic manner in the developed world. Pigs and wild boar constitute the primary Hepatitis E virus (HEV) zoonotic reservoir. Consumption of undercooked animal meat [...] Read more.

Hepatitis E is an emerging global disease, mainly transmitted via the fecal–oral route in developing countries, and in a zoonotic manner in the developed world. Pigs and wild boar constitute the primary Hepatitis E virus (HEV) zoonotic reservoir. Consumption of undercooked animal meat or direct contact with infected animals is the most common source of HEV infection in European countries. The purpose of this study is to develop an enzyme immunoassay (EIA) for the detection of anti-hepatitis E virus IgG in pig serum, using plant-produced recombinant HEV-3 ORF2 as an antigenic coating protein, and also to evaluate the sensitivity and specificity of this assay. A recombinant HEV-3 ORF2 110-610_6his capsid protein, transiently expressed by pEff vector in Nicotiana benthamiana plants was used to develop an in-house HEV EIA. The plant-derived HEV-3 ORF2 110-610_6his protein proved to be antigenically similar to the HEV ORF2 capsid protein and it can self-assemble into heterogeneous particulate structures. The optimal conditions for the in-house EIA (iEIA) were determined as follows: HEV-3 ORF2 110-610_6his antigen concentration (4 µg/mL), serum dilution (1:50), 3% BSA as a blocking agent, and secondary antibody dilution (1:20 000). The iEIA developed for this study showed a sensitivity of 97.1% (95% Cl: 89.9–99.65) and a specificity of 98.6% (95% Cl: 92.5–99.96) with a Youden index of 0.9571. A comparison between our iEIA and a commercial assay (PrioCHECK™ Porcine HEV Ab ELISA Kit, ThermoFisher Scientific, MA, USA) showed 97.8% agreement with a kappa index of 0.9399. The plant-based HEV-3 ORF2 iEIA assay was able to detect anti-HEV IgG in pig serum with a very good agreement compared to the commercially available kit. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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Review

Jump to: Research

15 pages, 5628 KiB

Open AccessReview

Plant-Based Vaccines: Antigen Design, Diversity, and Strategies for High Level Production

by Elizabeth Monreal-Escalante, Abel Ramos-Vega, Carlos Angulo and Bernardo Bañuelos-Hernández

Vaccines 2022, 10(1), 100; https://doi.org/10.3390/vaccines10010100 - 10 Jan 2022

Cited by 13 | Viewed by 8785

Abstract

Vaccines for human use have conventionally been developed by the production of (1) microbial pathogens in eggs or mammalian cells that are then inactivated, or (2) by the production of pathogen proteins in mammalian and insect cells that are purified for vaccine formulation, [...] Read more.

Vaccines for human use have conventionally been developed by the production of (1) microbial pathogens in eggs or mammalian cells that are then inactivated, or (2) by the production of pathogen proteins in mammalian and insect cells that are purified for vaccine formulation, as well as, more recently, (3) by using RNA or DNA fragments from pathogens. Another approach for recombinant antigen production in the last three decades has been the use of plants as biofactories. Only have few plant-produced vaccines been evaluated in clinical trials to fight against diseases, of which COVID-19 vaccines are the most recent to be FDA approved. In silico tools have accelerated vaccine design, which, combined with transitory antigen expression in plants, has led to the testing of promising prototypes in pre-clinical and clinical trials. Therefore, this review deals with a description of immunoinformatic tools and plant genetic engineering technologies used for antigen design (virus-like particles (VLP), subunit vaccines, VLP chimeras) and the main strategies for high antigen production levels. These key topics for plant-made vaccine development are discussed and perspectives are provided. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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11 pages, 618 KiB

Open AccessReview

Engineering Approaches in Plant Molecular Farming for Global Health

by Advaita Acarya Singh, Priyen Pillay and Tsepo Lebiletsa Tsekoa

Vaccines 2021, 9(11), 1270; https://doi.org/10.3390/vaccines9111270 - 3 Nov 2021

Cited by 8 | Viewed by 5479

Abstract

Since the demonstration of the first plant-produced proteins of medical interest, there has been significant growth and interest in the field of plant molecular farming, with plants now being considered a viable production platform for vaccines. Despite this interest and development by a [...] Read more.

Since the demonstration of the first plant-produced proteins of medical interest, there has been significant growth and interest in the field of plant molecular farming, with plants now being considered a viable production platform for vaccines. Despite this interest and development by a few biopharmaceutical companies, plant molecular farming is yet to be embraced by ‘big pharma’. The plant system offers a faster alternative, which is a potentially more cost-effective and scalable platform for the mass production of highly complex protein vaccines, owing to the high degree of similarity between the plant and mammalian secretory pathway. Here, we identify and address bottlenecks in the use of plants for vaccine manufacturing and discuss engineering approaches that demonstrate both the utility and versatility of the plant production system as a viable biomanufacturing platform for global health. Strategies for improving the yields and quality of plant-produced vaccines, as well as the incorporation of authentic posttranslational modifications that are essential to the functionality of these highly complex protein vaccines, will also be discussed. Case-by-case examples are considered for improving the production of functional protein-based vaccines. The combination of all these strategies provides a basis for the use of cutting-edge genome editing technology to create a general plant chassis with reduced host cell proteins, which is optimised for high-level protein production of vaccines with the correct posttranslational modifications. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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22 pages, 2525 KiB

Open AccessReview

Producing Vaccines against Enveloped Viruses in Plants: Making the Impossible, Difficult

by Hadrien Peyret, John F. C. Steele, Jae-Wan Jung, Eva C. Thuenemann, Yulia Meshcheriakova and George P. Lomonossoff

Vaccines 2021, 9(7), 780; https://doi.org/10.3390/vaccines9070780 - 13 Jul 2021

Cited by 22 | Viewed by 8640

Abstract

The past 30 years have seen the growth of plant molecular farming as an approach to the production of recombinant proteins for pharmaceutical and biotechnological uses. Much of this effort has focused on producing vaccine candidates against viral diseases, including those caused by [...] Read more.

The past 30 years have seen the growth of plant molecular farming as an approach to the production of recombinant proteins for pharmaceutical and biotechnological uses. Much of this effort has focused on producing vaccine candidates against viral diseases, including those caused by enveloped viruses. These represent a particular challenge given the difficulties associated with expressing and purifying membrane-bound proteins and achieving correct assembly. Despite this, there have been notable successes both from a biochemical and a clinical perspective, with a number of clinical trials showing great promise. This review will explore the history and current status of plant-produced vaccine candidates against enveloped viruses to date, with a particular focus on virus-like particles (VLPs), which mimic authentic virus structures but do not contain infectious genetic material. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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35 pages, 1741 KiB

Open AccessReview

Combating Human Viral Diseases: Will Plant-Based Vaccines Be the Answer?

by Srividhya Venkataraman, Kathleen Hefferon, Abdullah Makhzoum and Mounir Abouhaidar

Vaccines 2021, 9(7), 761; https://doi.org/10.3390/vaccines9070761 - 8 Jul 2021

Cited by 19 | Viewed by 7194

Abstract

Molecular pharming or the technology of application of plants and plant cell culture to manufacture high-value recombinant proteins has progressed a long way over the last three decades. Whether generated in transgenic plants by stable expression or in plant virus-based transient expression systems, [...] Read more.

Molecular pharming or the technology of application of plants and plant cell culture to manufacture high-value recombinant proteins has progressed a long way over the last three decades. Whether generated in transgenic plants by stable expression or in plant virus-based transient expression systems, biopharmaceuticals have been produced to combat several human viral diseases that have impacted the world in pandemic proportions. Plants have been variously employed in expressing a host of viral antigens as well as monoclonal antibodies. Many of these biopharmaceuticals have shown great promise in animal models and several of them have performed successfully in clinical trials. The current review elaborates the strategies and successes achieved in generating plant-derived vaccines to target several virus-induced health concerns including highly communicable infectious viral diseases. Importantly, plant-made biopharmaceuticals against hepatitis B virus (HBV), hepatitis C virus (HCV), the cancer-causing virus human papillomavirus (HPV), human immunodeficiency virus (HIV), influenza virus, zika virus, and the emerging respiratory virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have been discussed. The use of plant virus-derived nanoparticles (VNPs) and virus-like particles (VLPs) in generating plant-based vaccines are extensively addressed. The review closes with a critical look at the caveats of plant-based molecular pharming and future prospects towards further advancements in this technology. The use of biopharmed viral vaccines in human medicine and as part of emergency response vaccines and therapeutics in humans looks promising for the near future. Full article

(This article belongs to the Special Issue Plant Based Vaccines—A Powerhouse for Global Health 2.0)

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