Phase III: Randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18–49 years of age

Ward, Brian J.; Séguin, Annie; Couillard, Julie; Trépanier, Sonia; Landry, Nathalie

doi:10.1016/j.vaccine.2021.01.004

Cited by 50 publications

(32 citation statements)

References 28 publications

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“…The concept of plant-produced biopharmaceuticals and vaccines has been assessed and well explored by number of research groups worldwide. Several plant-produced therapeutics ( Kizhner et al, 2015 ; Ma et al, 2015 ; Mor, 2015 ; Prevail Ii Writing Group et al, 2016 ) and vaccines ( Yuki et al, 2013 ; Hendin et al, 2017 ; Donini and Marusic, 2019 ) are currently in pipeline for clinical trials and approval, Notably plant-produced Glucocerebrosidase enzyme (Elelyso TM ) for the treatment of type I Gaucher’s disease has been approved by US Food and Drug Administration ( Fox, 2012 ) and tobacco-derived seasonal flu VLP vaccine from Medicago Inc., is currently in final stages of clinical trial ( Ward et al, 2021 ). Hence, plant-based expression could be an alternative option for rapid production of emergency vaccines or therapeutic antibodies ( Iyappan et al, 2018 ; Diego-Martin et al, 2020 ; Rattanapisit et al, 2020 ; Shanmugaraj and Phoolcharoen, 2021 ; Siriwattananon et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Plant-Produced Receptor-Binding Domain of SARS-CoV-2 Elicits Potent Neutralizing Responses in Mice and Non-human Primates

Siriwattananon

Manopwisedjaroen

Shanmugaraj³

et al. 2021

Front. Plant Sci.

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The emergence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected global public health and economy. Despite the substantial efforts, only few vaccines are currently approved and some are in the different stages of clinical trials. As the disease rapidly spreads, an affordable and effective vaccine is urgently needed. In this study, we investigated the immunogenicity of plant-produced receptor-binding domain (RBD) of SARS-CoV-2 in order to use as a subunit vaccine. In this regard, RBD of SARS-CoV-2 was fused with Fc fragment of human IgG1 and transiently expressed in Nicotiana benthamiana by agroinfiltration. The plant-produced RBD-Fc fusion protein was purified from the crude extract by using protein A affinity column chromatography. Two intramuscular administration of plant-produced RBD-Fc protein formulated with alum as an adjuvant have elicited high neutralization titers in immunized mice and cynomolgus monkeys. Further it has induced a mixed Th1/Th2 immune responses and vaccine-specific T-lymphocyte responses which was confirmed by interferon-gamma (IFN-γ) enzyme-linked immunospot assay. Altogether, our results demonstrated that the plant-produced SARS-CoV-2 RBD has the potential to be used as an effective vaccine candidate against SARS-CoV-2. To our knowledge, this is the first report demonstrating the immunogenicity of plant-produced SARS-CoV-2 RBD protein in mice and non-human primates.

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Section: Discussionmentioning

confidence: 99%

Plant-Produced Receptor-Binding Domain of SARS-CoV-2 Elicits Potent Neutralizing Responses in Mice and Non-human Primates

Siriwattananon

Manopwisedjaroen

Shanmugaraj³

et al. 2021

Front. Plant Sci.

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“…In 2012, the program, in collaboration with Medicago, Canada, successfully manufactured 10 million doses of monovalent H1N1 VLP vaccine in tobacco plants within 30 days, accomplishing the proof-of-concept objective to demonstrate the potential scalability and rapidity of plant production to combat the influenza pandemic [41]. Numerous plant-based vaccines against a wide range of pathogens and diseases, including influenza, Ebola, rabies, hepatitis B, norovirus malaria, anthrax, and rotavirus, have entered different phases of clinical trials (Table 2) [27,36,48,50,58,59,62,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Recently, the quadrivalent vaccine developed by Medicago for seasonal influenza has completed a phase 3 clinical trial [48].…”

Section: Plant-based Vaccine Production For Epidemic Responsementioning

confidence: 99%

Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

Maharjan¹,

Choe

2021

Vaccines

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The prevalence of the coronavirus disease 2019 (COVID-19) pandemic in its second year has led to massive global human and economic losses. The high transmission rate and the emergence of diverse SARS-CoV-2 variants demand rapid and effective approaches to preventing the spread, diagnosing on time, and treating affected people. Several COVID-19 vaccines are being developed using different production systems, including plants, which promises the production of cheap, safe, stable, and effective vaccines. The potential of a plant-based system for rapid production at a commercial scale and for a quick response to an infectious disease outbreak has been demonstrated by the marketing of carrot-cell-produced taliglucerase alfa (Elelyso) for Gaucher disease and tobacco-produced monoclonal antibodies (ZMapp) for the 2014 Ebola outbreak. Currently, two plant-based COVID-19 vaccine candidates, coronavirus virus-like particle (CoVLP) and Kentucky Bioprocessing (KBP)-201, are in clinical trials, and many more are in the preclinical stage. Interim phase 2 clinical trial results have revealed the high safety and efficacy of the CoVLP vaccine, with 10 times more neutralizing antibody responses compared to those present in a convalescent patient’s plasma. The clinical trial of the CoVLP vaccine could be concluded by the end of 2021, and the vaccine could be available for public immunization thereafter. This review encapsulates the efforts made in plant-based COVID-19 vaccine development, the strategies and technologies implemented, and the progress accomplished in clinical trials and preclinical studies so far.

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“…Only recently, proof of lot-to-lot consistency of a plant-derived vaccine has been achieved in a clinical trial: three sequential lots of a quadrivalent virus-like particle influenza vaccine (QVLP) produced in N. benthamiana elicited equivalent antibody responses to the targeted hemagglutinin (HA) proteins in a phase III clinical trial. This analysis showed for the first time that a plant produced vaccine can meet the standard criteria for consistency of production [ 6 ].…”

Section: Simplified Industrial Production Of Vaccines In Plant By Combining Vlps and Genome Editingmentioning

confidence: 99%

“…Vaccines expressed in plants also have the benefit of no risk associated with the host DNA carried in a vaccine dose, given the phylogenetic distance between plant and human [ 6 ]. Thus, all the production steps aimed at minimizing the risk of host cell nucleic acid oncogenicity (i.e., reduction of DNA size to 100–200 base pairs in length), required for vaccines expressed in mammalian cell lines [ 141 ], can be reduced, decreasing the time, costs, and quality control tests.…”

Section: Other Advantages Of Plant-based Vaccine Productionmentioning

confidence: 99%

“…It also offers a potential solution to the scalability and cost-effectiveness of large-scale production of vaccines. Although plant-based human vaccines and monoclonals are not approved for the market yet, several vaccine candidates against bacteria, fungi, or viruses have been successfully produced in various plant systems and tested in preclinical models, for immunogenicity and safety, or under clinical trials, for safety and efficacy [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

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Frontiers in the Standardization of the Plant Platform for High Scale Production of Vaccines

Citiulo

Crosatti²,

Cattivelli³

et al. 2021

Plants

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The recent COVID-19 pandemic has highlighted the value of technologies that allow a fast setup and production of biopharmaceuticals in emergency situations. The plant factory system can provide a fast response to epidemics/pandemics. Thanks to their scalability and genome plasticity, plants represent advantageous platforms to produce vaccines. Plant systems imply less complicated production processes and quality controls with respect to mammalian and bacterial cells. The expression of vaccines in plants is based on transient or stable transformation systems and the recent progresses in genome editing techniques, based on the CRISPR/Cas method, allow the manipulation of DNA in an efficient, fast, and easy way by introducing specific modifications in specific sites of a genome. Nonetheless, CRISPR/Cas is far away from being fully exploited for vaccine expression in plants. In this review, an overview of the potential conjugation of the renewed vaccine technologies (i.e., virus-like particles - VLPs, and industrialization of the production process) with genome editing to produce vaccines in plants is reported, illustrating the potential advantages in the standardization of the plant platforms, with the overtaking of constancy of large-scale production challenges, facilitating regulatory requirements and expediting the release and commercialization of the vaccine products of genome edited plants.

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Phase III: Randomized observer-blind trial to evaluate lot-to-lot consistency of a new plant-derived quadrivalent virus like particle influenza vaccine in adults 18–49 years of age

Cited by 50 publications

References 28 publications

Plant-Produced Receptor-Binding Domain of SARS-CoV-2 Elicits Potent Neutralizing Responses in Mice and Non-human Primates

Plant-Produced Receptor-Binding Domain of SARS-CoV-2 Elicits Potent Neutralizing Responses in Mice and Non-human Primates

Plant-Based COVID-19 Vaccines: Current Status, Design, and Development Strategies of Candidate Vaccines

Frontiers in the Standardization of the Plant Platform for High Scale Production of Vaccines

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