Novel Transgenic Rice-Based Vaccines

Abstract

Oral vaccination can induce both systemic and mucosal antigen-specific immune responses. To control rampant mucosal infectious diseases, the development of new effective oral vaccines is needed. Plant-based vaccines are new candidates for oral vaccines, and have some advantages over the traditional vaccines in cost, safety, and scalability. Rice seeds are attractive for vaccine production because of their stability and resistance to digestion in the stomach. The efficacy of some rice-based vaccines for infectious, autoimmune, and other diseases has been already demonstrated in animal models. We reported the efficacy in mice, safety, and stability of a rice-based cholera toxin B subunit vaccine called MucoRice-CTB. To advance MucoRice-CTB for use in humans, we also examined its efficacy and safety in primates. The potential of transgenic rice production as a new mucosal vaccine delivery system is reviewed from the perspective of future development of effective oral vaccines.

Novel approaches for the design, delivery and administration of vaccine technologies

“…Once within the gastrointestinal tract, the cell wall is then broken down by microbes and the intracellular material is released [112]. These crops are staple foods in target vaccination areas, are inexpensive to produce and easy to grow in large quantities [114,115]. These transgenic cells may then be able to deliver antigenic material to the intestines, where it is free to interact with the gut-associated lymphoid tissue.…”

Current and New Approaches for Mucosal Vaccine Delivery

“…Plant-based oral vaccines have advantages over the traditional vaccines in cost, safety, and scalability. Since 1990, researchers have manufactured edible plant-based vaccines in carrot, soybean, tomato, rice, potato, and tobacco against microbial pathogen antigens such as the heat-labile toxin B subunit (LTB) of enterotoxigenic Escherichia coli, cholera toxin B subunit (CTB), and antigens from Yersinia pestis and viruses, such as hepatitis B virus, rotavirus, and Norwalk virus [159]. Many conventional vaccines are not widely distributed in developing countries where those vaccines are urgently needed, because of high production costs and the requirement of better infrastructure.…”

“…These results show that the MucoRice vaccine could be stockpiled longer at room temperature and could be widely used for oral vaccination without cold-chain management. Rice-based oral vaccine developments are under way against many infectious diseases and noninfectious diseases such as allergy, autoimmunity, and Alzheimer's disease [159].…”

Biomanufacturing of protective antibodies and other therapeutics in edible plant tissues for oral applications

“…One of the first was a vaccine candidate based on the heat-labile enterotoxin B (LTB) subunit of enterotoxigenic Escherichia coli (ETEC) produced in transgenic potato, which protected against an ETEC challenge in animal studies and was also immunogenic in humans during a phase I clinical trial (Haq et al, 1995;Mason et al, 1998;Tacket et al, 1998); the same was shown when it was produced in transgenic corn (Tacket, 2007;Tacket et al, 2004). Many examples for Alzheimer's disease, allergic diseases, or autoimmune and infectious diseases show that rice is one of the preferred EPTs for therapeutic protein production (Azegami et al, 2015;Takaiwa et al, 2015). A first example is the MucoRice-CTB, an oral vaccine against cholera, which consists of the antigen of the cholera toxin B (CTB) accumulating in rice seed storage organelles.…”

“…Edible plant tissues with GRAS status (such as fruits, seeds and certain leaves) can therefore be utilized as reservoirs of antibodies such as SIgAs for easy longtime storage and enabling quick availability after minimal processing when required for OPI. In the case of seeds, due to their low water content, they can be stored for years without losing antibody efficacy (Azegami et al, 2015;Virdi et al, 2013). If using more watery tissues, such as fleshy fruits and leaves, a step of lyophilization or spray-drying should be included prior to storing (Juarez et al, 2012;Su et al, 2015b).…”