Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection

Daisuke Tokuhara; Beatriz Álvarez; Mio Mejima; Tomoko Hiroiwa; Yuko Takahashi; Shiho Kurokawa; Masaharu Kuroda; Masaaki Oyama; Hiroko Kozuka-Hata; Tomonori Nochi; Hiroshi Sagara; Farah Aladin; Harold Marcotte; Leon G.J. Frenken; Miren Iturriza-Go'Mara; Hiroshi Kiyono; Lennart Hammarström; Yoshikazu Yuki

doi:10.1172/JCI70266

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection

Daisuke Tokuhara, Beatriz Álvarez, Mio Mejima, Tomoko Hiroiwa, Yuko Takahashi, Shiho Kurokawa, Masaharu Kuroda, Masaaki Oyama, Hiroko Kozuka-Hata, Tomonori Nochi, Hiroshi Sagara, Farah Aladin, Harold Marcotte, Leon G.J. Frenken, Miren Iturriza-Go'Mara, Hiroshi Kiyono, Lennart Hammarström, Yoshikazu Yuki^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

84 Citations (Scopus)

Abstract

Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, watersoluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

Original language	English
Pages (from-to)	3829-3838
Number of pages	10
Journal	Journal of Clinical Investigation
Volume	123
Issue number	9
DOIs	https://doi.org/10.1172/JCI70266
Publication status	Published - 3 Sept 2013

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10.1172/JCI70266

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Tokuhara, D., Álvarez, B., Mejima, M., Hiroiwa, T., Takahashi, Y., Kurokawa, S., Kuroda, M., Oyama, M., Kozuka-Hata, H., Nochi, T., Sagara, H., Aladin, F., Marcotte, H., Frenken, L. G. J., Iturriza-Go'Mara, M., Kiyono, H., Hammarström, L., & Yuki, Y. (2013). Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection. Journal of Clinical Investigation, 123(9), 3829-3838. https://doi.org/10.1172/JCI70266

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title = "Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection",

abstract = "Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, watersoluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.",

author = "Daisuke Tokuhara and Beatriz {\'A}lvarez and Mio Mejima and Tomoko Hiroiwa and Yuko Takahashi and Shiho Kurokawa and Masaharu Kuroda and Masaaki Oyama and Hiroko Kozuka-Hata and Tomonori Nochi and Hiroshi Sagara and Farah Aladin and Harold Marcotte and Frenken, {Leon G.J.} and Miren Iturriza-Go'Mara and Hiroshi Kiyono and Lennart Hammarstr{\"o}m and Yoshikazu Yuki",

year = "2013",

month = sep,

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doi = "10.1172/JCI70266",

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Tokuhara, D, Álvarez, B, Mejima, M, Hiroiwa, T, Takahashi, Y, Kurokawa, S, Kuroda, M, Oyama, M, Kozuka-Hata, H, Nochi, T, Sagara, H, Aladin, F, Marcotte, H, Frenken, LGJ, Iturriza-Go'Mara, M, Kiyono, H, Hammarström, L & Yuki, Y 2013, 'Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection', Journal of Clinical Investigation, vol. 123, no. 9, pp. 3829-3838. https://doi.org/10.1172/JCI70266

TY - JOUR

T1 - Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection

AU - Tokuhara, Daisuke

AU - Álvarez, Beatriz

AU - Mejima, Mio

AU - Hiroiwa, Tomoko

AU - Takahashi, Yuko

AU - Kurokawa, Shiho

AU - Kuroda, Masaharu

AU - Oyama, Masaaki

AU - Kozuka-Hata, Hiroko

AU - Nochi, Tomonori

AU - Sagara, Hiroshi

AU - Aladin, Farah

AU - Marcotte, Harold

AU - Frenken, Leon G.J.

AU - Iturriza-Go'Mara, Miren

AU - Kiyono, Hiroshi

AU - Hammarström, Lennart

AU - Yuki, Yoshikazu

PY - 2013/9/3

Y1 - 2013/9/3

N2 - Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, watersoluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

AB - Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, watersoluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

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AN - SCOPUS:84883532793

SN - 0021-9738

VL - 123

SP - 3829

EP - 3838

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 9

ER -

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection

Abstract

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