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

The Journal of Clinical Investigation August 8, 2013, Doi:10.1172/JCI70266
Daisuke Tokuhara1,2, Beatriz ρlvarez3, Mio Mejima1, Tomoko Hiroiwa1, Yuko Takahashi1, Shiho Kurokawa1, Masaharu Kuroda4, Masaaki Oyama5, Hiroko Kozuka-Hata5, Tomonori Nochi1, Hiroshi Sagara5, Farah Aladin6, Harold Marcotte3, Leon G.J. Frenken7, Miren Iturriza-Gómara8, Hiroshi Kiyono1,9, Lennart Hammarström3 and Yoshikazu Yuki1,9
1Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan. 2Department of Pediatrics, Osaka City University Graduate School of Medicine, Osaka, Japan. 3Division of Clinical Immunology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden. 4Crop Development Division, NARO Agriculture Research Center, Niigata, Japan. 5Medical Proteomics Laboratory, The Institute of Medical Science, University of Tokyo, Tokyo, Japan. 6Enteric Virus Unit, Virus Reference Department, Health Protection Agency, London, United Kingdom. 7Unilever Research and Development Vlaardingen BV, Vlaardingen, Netherlands. 8Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. 9International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

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.