Plant glycoengineering for designing next-generation vaccines and therapeutic proteins

Strasser, Richard

doi:10.1016/j.biotechadv.2023.108197

Cited by 17 publications

(8 citation statements)

References 185 publications

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“…N -glycosylation results in a complex mixture of neutral and monosialylated multiantennary N -glycans, accounting for nearly half of the molecular mass of mature glycoproteins ( Branza-Nichita et al, 2004 ; Gavrilov et al, 2011 ). Interestingly, in terms of N -glycosylation, a previous study ( Strasser, 2023 ) reported that N. benthamiana plant-based expression platforms exhibit remarkable versatility in that they can effectively accommodate transient and stable engineering of the N -glycan processing pathways without inducing cell death or generating adverse growth phenotypes associated with biomass production, protein expression or yield, features lacking in conventional expression systems. In this study, protein expression using a plant-derived system was employed as a first report for E rns protein expression in which the yielded E rns protein had a molecular mass of ~45 kDa, comparable to the mature E rns protein in previous studies ( Thiel et al, 1991 ; Bhattacharya et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, N. benthamiana also possesses a robust protein folding and posttranslational modification machinery, allowing for the production of complex, biologically active proteins. A key advantage of N. benthamiana is its ability to produce glycosylated proteins with mammalian-like glycosylation patterns which is particularly advantageous for producing therapeutic proteins because proper glycosylation is often critical for protein stability, functionality, and immunogenicity ( Strasser, 2023 ). Therefore, N. benthamiana -based expression system highlight their advantages, applications, and prospects.…”

Section: Introductionmentioning

confidence: 99%

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Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever

Huynh,

Sohn,

Park

et al. 2024

Front. Microbiol.

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BackgroundIt is essential to consider a practical antibody test to successfully implement marker vaccines and validate vaccination efficacy against classical swine fever virus (CSFV). The test should include a serological antibody assay, combined with a tool for differentiating infected from vaccinated animals (DIVA). The immunochromatographic test strip (ICS) has been exclusively designed for detecting CSFV E2 antibodies while lacking in detecting Erns antibodies, which can be employed and satisfy DIVA strategy. This study developed a novel ICS for detecting CSFV E2/Erns dual-antibody. The effectiveness of ICS in evaluating the DIVA capability of two novel chimeric pestivirus vaccine candidates was assessed.MethodsRecombinant E2 or Erns protein was transiently expressed in the plant benthamiana using Agrobacterium tumefaciens. ICS was subsequently assembled, and goat anti-rabbit IgG and recombinant CSFV E2 or Erns protein were plated onto the nitrocellulose membrane as control and test lines, respectively. The sensitivity and specificity of ICS were evaluated using sera with different neutralizing antibody titers or positive for antibodies against CSFV and other pestiviruses. The coincidence rates for detecting E2 and Erns antibodies between ICS and commercial enzyme-linked immunosorbent assay (ELISA) kits were also computed. ICS performance for DIVA capability was evaluated using sera from pigs vaccinated with conventional vaccine or chimeric vaccine candidates.ResultsE2 and Erns proteins were successfully expressed in N. benthamiana-produced recombinant proteins. ICS demonstrated high sensitivity in identifying CSFV E2 and Erns antibodies, even at the low neutralizing antibody titers. No cross-reactivity with antibodies from other pestiviruses was confirmed using ICS. There were high agreement rates of 93.0 and 96.5% between ICS and two commercial ELISA kits for E2 antibody testing. ICS also achieved strong coincidence rates of 92.9 and 89.3% with two ELISA kits for Erns antibody detection. ICS confirmed the absence of CSFV Erns-specific antibodies in sera from pigs vaccinated with chimeric vaccine candidates.ConclusionE2 and Erns proteins derived from the plant showed great potential and can be used to engineer a CSFV E2/Erns dual-antibody ICS. The ICS was also highly sensitive and specific for detecting CSFV E2 and Erns antibodies. Significantly, ICS can fulfill the DIVA concept by incorporating chimeric vaccine candidates.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever

Huynh,

Sohn,

Park

et al. 2024

Front. Microbiol.

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“…Another possibility is to use plant expression systems that present the advantage to allow the production of recombinant glycoproteins ( 165 ). Active recombinant human and mouse cytokines have been successfully produced in rice seeds, with low endotoxin contamination ( 166 ).…”

Section: Other Solutions For Recombinant Proteins Expression and Puri...mentioning

confidence: 99%

The dangerous liaisons in innate immunity involving recombinant proteins and endotoxins: Examples from the literature and the Leptospira field

Bonhomme,

Cavaillon,

Werts

2024

Journal of Biological Chemistry

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“…A complex metabolic network and many glycosylation pathways are used during the enzymatic glycosylation of proteins to produce a wide variety of proteoforms ( Schjoldager et al., 2020 ). For instance in humans, N-acetylglucosaminyl transferases IV and V present in Golgi functions in galactosylation, branch elongation and sialic acid capping, which is not found in plants ( Strasser, 2022 ; Strasser, 2023 ). In order to produce therapeutic proteins of interest in plant with desired glycosylation pattern, β-1,4 galactosyl transferase co-expression and sub-cellular localization to Golgi is preferred ( Navarre et al., 2017 ; Strasser, 2022 ).…”

Section: Systems Engineering Approaches To Produce Recombinant Biopha...mentioning

confidence: 99%

Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals

Parthiban,

Vijeesh,

Gayathri

et al. 2023

Front. Plant Sci.

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Recombinant biopharmaceuticals including antigens, antibodies, hormones, cytokines, single-chain variable fragments, and peptides have been used as vaccines, diagnostics and therapeutics. Plant molecular pharming is a robust platform that uses plants as an expression system to produce simple and complex recombinant biopharmaceuticals on a large scale. Plant system has several advantages over other host systems such as humanized expression, glycosylation, scalability, reduced risk of human or animal pathogenic contaminants, rapid and cost-effective production. Despite many advantages, the expression of recombinant proteins in plant system is hindered by some factors such as non-human post-translational modifications, protein misfolding, conformation changes and instability. Artificial intelligence (AI) plays a vital role in various fields of biotechnology and in the aspect of plant molecular pharming, a significant increase in yield and stability can be achieved with the intervention of AI-based multi-approach to overcome the hindrance factors. Current limitations of plant-based recombinant biopharmaceutical production can be circumvented with the aid of synthetic biology tools and AI algorithms in plant-based glycan engineering for protein folding, stability, viability, catalytic activity and organelle targeting. The AI models, including but not limited to, neural network, support vector machines, linear regression, Gaussian process and regressor ensemble, work by predicting the training and experimental data sets to design and validate the protein structures thereby optimizing properties such as thermostability, catalytic activity, antibody affinity, and protein folding. This review focuses on, integrating systems engineering approaches and AI-based machine learning and deep learning algorithms in protein engineering and host engineering to augment protein production in plant systems to meet the ever-expanding therapeutics market.

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Plant glycoengineering for designing next-generation vaccines and therapeutic proteins

Cited by 17 publications

References 185 publications

Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever

Development of a dual immunochromatographic test strip to detect E2 and Erns antibodies against classical swine fever

The dangerous liaisons in innate immunity involving recombinant proteins and endotoxins: Examples from the literature and the Leptospira field

Artificial intelligence-driven systems engineering for next-generation plant-derived biopharmaceuticals

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