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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container_end_page 3838
container_issue 9
container_start_page 3829
container_title The Journal of clinical investigation
container_volume 123
creator 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
description 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.
doi_str_mv 10.1172/jci70266
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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 (&gt;1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. 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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 (&gt;1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. 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source MEDLINE; SWEPUB Freely available online; Journals@Ovid Complete; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection
subjects Administration, Oral
Age
Agricultural biotechnology
Animals
Antibiotic Prophylaxis
Antibodies, Neutralizing - administration & dosage
Antibodies, Neutralizing - biosynthesis
Antibodies, Viral - administration & dosage
Antibodies, Viral - biosynthesis
Antiviral Agents - administration & dosage
Biomedical research
Care and treatment
Clinical trials
Diarrhea
Diarrhea - immunology
Diarrhea - prevention & control
Diarrhea - virology
Humans
Industrialized nations
Intestine, Small - pathology
Intestine, Small - virology
Medical research
Medicin och hälsovetenskap
Mice
Mice, Inbred BALB C
Mice, SCID
Oryza - genetics
Oryza - metabolism
Oryza sativa
Plants, Genetically Modified - genetics
Plants, Genetically Modified - metabolism
Preventive medicine
Protein Stability
Proteins
Rotavirus
Rotavirus - immunology
Rotavirus infections
Rotavirus Infections - immunology
Rotavirus Infections - prevention & control
Rotavirus Infections - virology
Scholarships & fellowships
Science
Seeds
Seeds - genetics
Seeds - metabolism
Single-Chain Antibodies - administration & dosage
Single-Chain Antibodies - biosynthesis
Solubility
Vaccines
Virus Shedding
Viruses
Yeast
title Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection
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