Development of rice-based oral antibody therapy against rotavirus infections
Institute of Medical Science
Rotavirus is leading cause of diarrhea in infants worldwide, causing 114 million episodes of diarrhea annually in children in under the age of five. Two licensed rotavirus vaccines are currently available. However, there is still a need for alternative strategies in situations including outbreak and disaster, and infants who are in immunocompromised state or miss the narrow age-window for vaccination.
Assistant Professor Yoshikazu Yuki and research resident Daisuke Tokuhara (currently Lecturer at Osaka City University Graduate School) and their group at the Institute of Medical Science, the University of Tokyo have developed a novel system for prophylaxis and therapy against rotavirus infections using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (nanobody; code name ARP1). The rice-based nanobody (named as MucoRice-ARP1) was produced at high levels in rice seeds and extracted easily as a soluble form by water. MucoRice-ARP1 retained in vitro neutralizing activity after long-term storage for more than one year and boiling, and conferred protection in mice even after heat treatment at 94oC for 30 min.
This high-yield, water-soluble and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections. MucoRice-ARP1 offers a novel approach to the prevention and treatment of rotavirus-induced diarrhea in outbreak of disaster situations and may provide an alternative to vaccination in individuals in whom current vaccines are contraindicated. This technology can also be extended to the production of antibody fragments against other enteric pathogens such as norovirus, and may also be applicable to intestinal diseases beyond infections.
Press release (Japanese)
Daisuke Tokuhara, Beatriz Alvarez, Masaharu Kuroda, Masaaki Oyama, ,Harold Marcotte, Leon G.J. Frenken, Miren Iturriza-Gomara, Hiroshi Kiyono, Lennart Hammarstrom, Yoshikazu Yuki,
“Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection”,
The Journal of Clinical Investigation 2013/08/09, doi: 10.1172/JCI70266.