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Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection
Daisuke Tokuhara, … , Lennart Hammarström, Yoshikazu Yuki
Daisuke Tokuhara, … , Lennart Hammarström, Yoshikazu Yuki
Published August 8, 2013
Citation Information: J Clin Invest. 2013;123(9):3829-3838. https://doi.org/10.1172/JCI70266.
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Research Article Infectious disease

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

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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, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

Authors

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-Gómara, Hiroshi Kiyono, Lennart Hammarström, Yoshikazu Yuki

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Figure 2

Neutralizing activity of MucoRice-ARP1 against human RV strains.

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Neutralizing activity of MucoRice-ARP1 against human RV strains.
Neutral...
Neutralizing activity of ARP1 samples from different origins and HBC against the human RV strains Wa (G1P[8]), ST-3 (G4P[6]), 69M (G8P[10]), F45 (G9P[8]) and Va70 (G4P[8]) using 2-fold dilutions of MucoRice-ARP1 containing rice water (shown as MucoRice-ARP1), WT rice (used as a negative control), ARP1 purified from yeast (shown as yeast-ARP1), and HBC. Lines indicate the percentage of infected cells related to control wells infected in the absence of added proteins. The horizontal line at 40% infected cells indicates a reduction of 60% in the infectivity of the RV strains.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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