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

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, watersoluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

Delivery strategies to enhance oral vaccination against enteric infections

“…CTB found in MucoRice is localized inside protein bodies within the rice grains, therefore providing protection from the harsh environment of the GIT and thus MucoRice acts in a similar fashion to a capsule for the delivery of CTB to gut inductive sites [221]. A similar rice-based oral vaccine against rotavirus has also shown promise in murine studies [223]. Human trials will in time reveal if such a system can indeed provide a sustainable solution to eradicating enteric diarrhea.…”

Potent In Vitro and In Vivo Activity of Plantibody Specific for Porphyromonas gingivalis FimA

“…Transgenic plants or transient production systems in plants have been used to generate MAbs that can specifically bind to antigens or pathogens and protect the host from infection via passive immunization (15,16). The advantages of MAb manufacturing in transgenic plants include large-scale production, low cost, and reduction of health risks that arise from contamination with human pathogens or toxins (17).…”

Camelid nanobodies with high affinity for broad bean mottle virus: a possible promising tool to immunomodulate plant resistance against viruses

“…We hypothesized that scFv expression in plants might be a limiting factor and that single domain antibodies or nanobodies might be a better option. Although the production of significant amounts of nanobodies in seeds has recently been indicated (Tokuhara et al 2013;De Buck et al 2012), the ectopic expression of nanobodies in planta for virus attenuation is lacking (De Meyer et al 2014b). Note that nanobodies (from alpaca) against Tulip virus X were only developed for diagnostic purposes (Beekwilder et al 2008).…”

“…Furthermore, the minimal-sized monomeric nanobodies and their ability to bind epitopes that are cryptic or not accessible to conventional antibodies offer special advantages (Hassanzadeh-Ghassabeh et al 2013). So far, multiple nanobodies have been successfully generated against numerous human and animal pathogens including protozoan parasites, bacteria and viruses (Wesolowski et al 2009;Tokuhara et al 2013;Desmyter et al 2013;Vanlandschoot et al 2011). Several recent reports have indicated the great potential of plants as efficient bioreactors for nanobody production (Jobling et al 2003;Ismaili et al 2007;Winichayakul et al 2009;Teh and Kavanagh 2010;Tokuhara et al 2013;De Buck et al 2013;De Meyer et al 2014a, b).…”