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

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-specifi...

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Veröffentlicht in:The Journal of clinical investigation 2013-09, Vol.123 (9), p.3829-3838
Hauptverfasser: Tokuhara, Daisuke, Álvarez, Beatriz, Mejima, Mio, Hiroiwa, Tomoko, Takahashi, Yuko, Kurokawa, Shiho, Kuroda, Masaharu, Oyama, Masaaki, Kozuka-Hata, Hiroko, Nochi, Tomonori, Sagara, Hiroshi, Aladin, Farah, Marcotte, Harold, Frenken, Leon G J, Iturriza-Gómara, Miren, Kiyono, Hiroshi, Hammarström, Lennart, Yuki, Yoshikazu
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Sprache:eng
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Zusammenfassung: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.
ISSN:0021-9738
1558-8238
1558-8238
DOI:10.1172/jci70266