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

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 4

Histopathological examination and quantification of RV in the small intestine after RRV-induced diarrhea.

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Histopathological examination and quantification of RV in the small inte...
(A–D) Histological sections of small intestine ileal mucosa from a noninfected mouse treated with PBS (A), RRV-infected mouse treated with PBS (B), RRV-infected mouse treated with MucoRice-ARP1 (C), and RRV-infected mouse treated with WT rice extract (D). In the RRV-infected mouse pups treated with PBS (B) or WT rice extract (D), large vacuoles are seen in the enterocytes lining the surface of the villous tips in the ileum. Histopathological lesions were absent in noninfected control mice (A) and pups treated with MucoRice-ARP1 (C). Sections were stained with H&E. Scale bars: 100 μm. (E) Quantification of RV in the small intestine after MucoRice-ARP1 treatment. Results are given as VP7 RNA copies per weight (mg) of small intestine. Bars indicate the median RV load for each group of animals. Differences in virus load between the MucoRice-ARP1–treated group and the WT rice-fed group or PBS-treated (RRV alone) group were evaluated using the Kruskal-Wallis test followed by the Mann-Whitney U test.