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

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

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Key message: The first Good Manufacturing Practices production of a purification-free rice-based oral cholera vaccine (MucoRice-CTB) from transgenic plants in a closed cultivation system yielded a product meeting regulatory requirements. Abstract: Despite our knowledge of their advantages, plant-based vaccines remain unavailable for human use in both developing and industrialized countries. A leading, practical obstacle to their widespread use is producing plant-based vaccines that meet governmental regulatory requirements. Here, we report the first production according to current Good Manufacturing Practices of a rice-based vaccine, the cholera vaccine MucoRice-CTB, at an academic institution. To this end, we established specifications and methods for the master seed bank (MSB) of MucoRice-CTB, which was previously generated as a selection-marker-free line, evaluated its propagation, and given that the stored seeds must be renewed periodically. The production of MucoRice-CTB incorporated a closed hydroponic system for cultivating the transgenic plants, to minimize variations in expression and quality during vaccine manufacture. This type of molecular farming factory can be operated year-round, generating three harvests annually, and is cost- and production-effective. Rice was polished to a ratio of 95 % and then powdered to produce the MucoRice-CTB drug substance, and the identity, potency, and safety of the MucoRice-CTB product met pre-established release requirements. The formulation of MucoRice-CTB made by fine-powdering of drug substance and packaged in an aluminum pouch is being evaluated in a physician-initiated phase I study.

Original languageEnglish
Pages (from-to)667-679
Number of pages13
JournalPlant Cell Reports
Volume35
Issue number3
DOIs
Publication statusPublished - 2016 Mar 1
Externally publishedYes

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Keywords

  • GMP production
  • Molecular farming
  • MucoRice
  • Oral vaccine
  • Seed bank

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Plant Science

Cite this

Kashima, K., Yuki, Y., Mejima, M., Kurokawa, S., Suzuki, Y., Minakawa, S., Takeyama, N., Fukuyama, Y., Azegami, T., Tanimoto, T., Kuroda, M., Tamura, M., Gomi, Y., & Kiyono, H. (2016). Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants. Plant Cell Reports, 35(3), 667-679. https://doi.org/10.1007/s00299-015-1911-9