Rice seed for delivery of vaccines to gut mucosal immune tissues

Abstract

SummaryGut-associated lymphoid tissue (GALT) is the biggest lymphoid organ in the body. It plays a role in robust immune responses against invading pathogens while maintaining immune tolerance against nonpathogenic antigens such as foods. Oral vaccination can induce mucosal and systemic antigen-specific immune reactions and has several advantages including ease of administration, no requirement for purification and ease of scale-up of antigen. Thus far, taking advantage of these properties, various plant-based oral vaccines have been developed. Seeds provide a superior production platform over other plant tissues for oral vaccines; they offer a suitable delivery vehicle to GALT due to their high stability at room temperature, ample and stable deposition space, high expression level, and protection from digestive enzymes in gut. A rice seed production system for oral vaccines was established by combining stable deposition in protein bodies or protein storage vacuoles and enhanced endosperm-specific expression. Various types of rice-based oral vaccines for infectious and allergic diseases were generated. Efficacy of these rice-based vaccines was evaluated in animal models.

Production of BP178, a derivative of the synthetic antibacterial peptide BP100, in the rice seed endosperm

“…It is known that both glutelin and globulin rice seed storage proteins are synthesized in the endoplasmic reticulum and deposited in the PBII (also called protein storage vacuoles, [57]) of rice endosperm, due to cis-acting RNA localization signals present in the transcripts [58]. However, the sorting signals for seed storage proteins deposition into PBII have not yet been identified in rice [59]. Our results illustrate the utility of using an endosperm-specific promoter and signal peptide sequence of seed storage proteins for production of BP178 in protein body enriched fractions of transgenic rice seed.…”

RNA Interference-Mediated Simultaneous Suppression of Seed Storage Proteins in Rice Grains

“…Recently, it has been suggested that the seed is a good platform for producing valuable recombinant proteins due to multiple advantages, such as high productivity, long-term storage stability, and low-cost oral delivery of therapeutic proteins (Takaiwa et al, 2015). However, as a downside, the accumulation of some recombinant proteins in the endosperm of transgenic rice seeds results in chalky and shriveled phenotypes.…”

Oral Administration of a Seed-based Bivalent Rotavirus Vaccine Containing VP6 and NSP4 Induces Specific Immune Responses in Mice

“…Proteins restricted to the ER can avoid being glycosylated by the Golgi apparatus with plant-specific α-1,3-fucose and β-1,2-xylose residues that might be immunogenic in humans (Garcia-Casado et al, 1996; Yang et al, 2008). Furthermore, ER and its derived protein body (PB-I) can prevent the hydrolysis of exogenous proteins and improve their accumulation (Takaiwa et al, 2015). …”

“…Furthermore, VP6 and LTB-NSP4 were located in the endoplasmic reticulum in this study. Proteins with ER retention signals expressed in maize or rice seed usually accumulate in the ER and its derived PB-I (Takaiwa et al, 2015). This is important in the prevention of post-translational N-glycosylation by the Golgi apparatus, which contains the carbohydrate groups α-1,3-fucose and β-1,2-xylose.…”

“…Thus, plant seeds, especially from rice and maize, offer another option for protein level improvement. Seeds have protein bodies (PBs) and protein storage vacuoles (PSVs) where exogenous proteins can accumulate and avoid hydrolysis (Takaiwa et al, 2015). The MucoRice-based expression system has high levels of target protein, high heat stability, long term storage stability and an efficient immune response (Nochi et al, 2007; Tokuhara et al, 2013).…”