Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants

Kashima, Koji; Yuki, Yoshikazu; Mejima, Mio; Kurokawa, Shiho; Suzuki, Yuji; Minakawa, Satomi; Takeyama, Natsumi; Fukuyama, Yoshiko; Azegami, Tatsuhiko; Tanimoto, Tsuyoshi; Kuroda, Masaharu; Tamura, Minoru; Gomi, Yasuo; Kiyono, Hiroshi

doi:10.1007/s00299-015-1911-9

Cited by 38 publications

(31 citation statements)

References 26 publications

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“…Recently, we have developed and established Good Manufacturing Practice-compliant procedures for the generation of the purification-free oral MucoRice-CTB vaccine in a closed production system and have characterized specification and test methods to ensure the quality of the vaccine product 15 . MucoRice-CTB produced in the system was evaluated in a phase I study of MucoRice-CTB conducted with healthy volunteers at a hospital affiliated with the Institute of Medical Science, the University of Tokyo.…”

Section: Discussionmentioning

confidence: 99%

“…Seedling growth, cultivation, and seed drying and processing were as previously described 15 with slight modifications. Briefly, MR-CTB51A and NPB seeds were sterilized and soaked in water (pH adjusted to 5.0–5.5) in a growth chamber (MLR-352; Panasonic Healthcare Co., Ltd., Tokyo, Japan) set at 16 h light (26 °C)/8 h dark (24 °C), 300–400 μmol mβ −2 s −1 light intensity, for 21 days.…”

Section: Methodsmentioning

confidence: 99%

“…The vaccine has been improved by introducing an Asn-to-Gln substitution at the 4th position of the CTB protein (to eliminate plant-specific glycosylation and thus obtain a uniform CTB protein), by removing the selectable marker cassette, and by introducing an RNA interference (RNAi) cassette (to down-regulate endogenous seed storage proteins) 7–9, 12–14 . MucoRice-CTB is a powder prepared from rice (polished to a ratio of 95%) from the MucoRice-CTB transgenic rice line 51A (MR-CTB51A); it was evaluated in a physician-initiated phase I study with healthy volunteers at the Research Hospital of the Institute of Medical Science, the University of Tokyo 15 . A comparative whole-genome analysis using next-generation sequencing demonstrated that MucoRice-CTB transgenic lines (including MR-CTB51A) and their parental non-transgenic lines ( O .…”

Section: Introductionmentioning

confidence: 99%

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Seed Metabolome Analysis of a Transgenic Rice Line Expressing Cholera Toxin B-subunit

Ogawa

Kashima

Yuki

et al. 2017

Sci Rep

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Plant-based human vaccines have been actively developed in recent years, and rice (Oryza sativa L.) is one of the best candidate crops for their production and delivery. By expressing a modified cholera toxin B (CTB) subunit, we previously developed MucoRice-CTB, a rice-based vaccine against cholera, which is caused by infection of the intestine with the bacteria Vibrio cholerae. MucoRice-CTB lines have been extensively characterized by whole-genome sequencing and proteome analyses to evaluate the mutation profiles and proteome status, respectively. Here, we report non-targeted metabolomic profiling of the MucoRice-CTB transgenic rice line 51A (MR-CTB51A), MucoRice-RNAi (MR-RNAi), and their non-transgenic parent line by using gas chromatography–time-of-flight mass spectrometry. The levels of several amino acids, organic acids, carbohydrates, lipids, and secondary metabolites were significantly increased in MR-CTB51A compared with the non-transgenic parent line. These metabolomics results complement essential information obtained by genome sequencing and proteomics approaches, thereby contributing to comprehensive understanding of the properties of MucoRice-CTB as a plant-based vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Seed Metabolome Analysis of a Transgenic Rice Line Expressing Cholera Toxin B-subunit

Ogawa

Kashima

Yuki

et al. 2017

Sci Rep

Self Cite

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“…To ensure GMP, a rice-based oral vaccine against cholera, MucoRice-CTB, was produced in a closed hydroponic cultivation system, thereby yielding a product that met regulatory requirements [117]. These plants were cultivated using hydroponic techniques based on a circulating nutrient solution and a polystyrene foam board as a floating holder in a molecular farming factory that can be harvested three times a year.…”

Section: Hydroponic Systemsmentioning

confidence: 99%

Development of Systems for the Production of Plant-Derived Biopharmaceuticals

Moon

Park

et al. 2019

Plants

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Over the last several decades, plants have been developed as a platform for the production of useful recombinant proteins due to a number of advantages, including rapid production and scalability, the ability to produce unique glycoforms, and the intrinsic safety of food crops. The expression methods used to produce target proteins are divided into stable and transient systems depending on applications that use whole plants or minimally processed forms. In the early stages of research, stable expression systems were mostly used; however, in recent years, transient expression systems have been preferred. The production of the plant itself, which produces recombinant proteins, is currently divided into two major approaches, open-field cultivation and closed-indoor systems. The latter encompasses such regimes as greenhouses, vertical farming units, cell bioreactors, and hydroponic systems. Various aspects of each system will be discussed in this review, which focuses mainly on practical examples and commercially feasible approaches.

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“…The rice produced was polished, powdered, and packaged to make the MucoRice-CTB drug substance. Final check on the identity, potency, and safety of MucoRice-CTB product must be conducted and only the products that met the quality requirements will be released [86].…”

Section: Manufacturing Of Vaccines According To Gmp Proceduresmentioning

confidence: 99%

Plant-Based Vaccines: Production and Challenges

et al. 2016

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Plant-based vaccine technologies involve the integration of the desired genes encoding the antigen protein for specific disease into the genome of plant tissues by various methods. Agrobacterium-mediated gene transfer and transformation via genetically modified plant virus are the common methods that have been used to produce effective vaccines. Nevertheless, with the advancement of science and technology, new approaches have been developed to increase the efficiency of former methods such as biolistic, electroporation, agroinfiltration, sonication, and polyethylene glycol treatment. Even though plant-based vaccines provide many benefits to the vaccine industry, there are still challenges that limit the rate of successful production of these third-generation vaccines. Even with all the limitations, continuous efforts are still ongoing in order to produce efficient vaccine for many human and animals related diseases owing to its great potentials. This paper reviews the existing conventional methods as well as the development efforts by researchers in order to improve the production of plant-based vaccines. Several challenges encountered during and after the production process were also discussed.

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Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants

Cited by 38 publications

References 26 publications

Seed Metabolome Analysis of a Transgenic Rice Line Expressing Cholera Toxin B-subunit

Seed Metabolome Analysis of a Transgenic Rice Line Expressing Cholera Toxin B-subunit

Development of Systems for the Production of Plant-Derived Biopharmaceuticals

Plant-Based Vaccines: Production and Challenges

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