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 5

Inhibition of viral shedding after MucoRice-ARP1 treatment in SCID mice with chronic RRV infection.

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Inhibition of viral shedding after MucoRice-ARP1 treatment in SCID mice ...
(A–D) MucoRice-ARP1 powder (200 mg) containing 1.7 mg of ARP1 was intragastrically administered to mice twice daily for 7 days. Fecal samples were collected on days –1, 1, 3, 9, and 14 (n = 6, each group). Control feces were collected from noninfected SCID mice. Positive control feces were collected from RRV-inoculated SCID adult mice treated with PBS. Bars indicate the median RV shedding level for each group of animals. Results are given as VP7 RNA copies per mg of stool. MucoRice-ARP1–treated mice showed a significantly lower amount of VP7 RNA copies on day 3 (*P = 0.002) and day 9 (**P = 0.003) compared with WT rice–treated or PBS-treated mice. Statistical significance among groups was calculated using the Kruskal-Wallis test followed by the Mann-Whitney U test.