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-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.
Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.
Daisuke
D
Tokuhara
Beatriz
B
Álvarez
Mio
M
Mejima
Tomoko
T
Hiroiwa
Yuko
Y
Takahashi
Shiho
S
Kurokawa
Masaharu
M
Kuroda
Masaaki
M
Oyama
Hiroko
H
Kozuka-Hata
Tomonori
T
Nochi
Hiroshi
H
Sagara
Farah
F
Aladin
Harold
H
Marcotte
Leon G J
LG
Frenken
Miren
M
Iturriza-Gómara
Hiroshi
H
Kiyono
Lennart
L
Hammarström
Yoshikazu
Y
Yuki
D000284:Administration, Oral; D000818:Animals; D019072:Antibiotic Prophylaxis; D057134:Antibodies, Neutralizing / Q000008:administration & dosage* / Q000096:biosynthesis; D000914:Antibodies, Viral / Q000008:administration & dosage* / Q000096:biosynthesis; D000998:Antiviral Agents / Q000008:administration & dosage*; D003967:Diarrhea / Q000276:immunology / Q000517:prevention & control / Q000821:virology; D006801:Humans; D007421:Intestine, Small / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D012275:Oryza / Q000235:genetics / Q000378:metabolism*; D030821:Plants, Genetically Modified / Q000235:genetics / Q000378:metabolism; D055550:Protein Stability; D012401:Rotavirus / Q000276:immunology; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D012639:Seeds / Q000235:genetics / Q000378:metabolism; D057127:Single-Chain Antibodies / Q000008:administration & dosage / Q000096:biosynthesis; D012995:Solubility; D017201:Virus Shedding
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000998:Antiviral Agents; D057127:Single-Chain Antibodies