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

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

doi:10.1172/JCI70266

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

J Clin Invest. 2013 Sep;123(9):3829-38. doi: 10.1172/JCI70266. Epub 2013 Aug 8.

Authors

Daisuke Tokuhara¹, 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

Affiliation

¹ Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Antibiotic Prophylaxis*
Antibodies, Neutralizing / administration & dosage*
Antibodies, Neutralizing / biosynthesis
Antibodies, Viral / administration & dosage*
Antibodies, Viral / biosynthesis
Antiviral Agents / administration & dosage*
Diarrhea / immunology
Diarrhea / prevention & control
Diarrhea / virology
Humans
Intestine, Small / pathology
Intestine, Small / virology
Mice
Mice, Inbred BALB C
Mice, SCID
Oryza / genetics
Oryza / metabolism*
Plants, Genetically Modified / genetics
Plants, Genetically Modified / metabolism
Protein Stability
Rotavirus / immunology
Rotavirus Infections / immunology
Rotavirus Infections / prevention & control*
Rotavirus Infections / virology
Seeds / genetics
Seeds / metabolism
Single-Chain Antibodies / administration & dosage
Single-Chain Antibodies / biosynthesis
Solubility
Virus Shedding

Substances

Antibodies, Neutralizing
Antibodies, Viral
Antiviral Agents
Single-Chain Antibodies