One of the most significant limitations faced when developing new vaccine formulations for human use is the lack of safe, efficacious adjuvants that can be combined with promising new vaccine candidates to stimulate a protective host response, in the absence of safe, efficacious adjuvants that can be combined with these new vaccine candidates, the vaccine, by itself, is often not sufficient to protect individuals from a particular microbial disease. This is especially true for the development of subunit vaccines that use a single protein isolated from a microbial pathogen in an attempt to protect individuals from viral, bacterial, or fungal pathogens. These subunit vaccines are often very safe since they do not cause any infection and since they have fewer side effects than attenuated or killed microbes sometimes used in vaccine formulations. However there is one significant limitation in using these safer subunit vaccines. By themselves, the microbial proteins often do a poor job at stimulating human immune responses unless a vaccine formulation containing a strong adjuvant is used, especially when trying to stimulate a protective, mucosal response. In this grant application, Drs. Bost, Piller and Clemente propose to demonstrate the feasibility of developing an edible adjuvant expressed in transgenic plants. These novel studies focus on the use of a known adjuvant, the E. coil heat labile toxin (LT), and its expression in soybeans. A non-toxic form of this bacterial protein, which has potent adjuvant activity, will be expressed in soybeans, and its ability to function as an adjuvant following oral consumption will be demonstrated using a mouse immunization model. If successful, this work will provide an efficient expression system for production of large quantities of an edible adjuvant which is cost-effective to produce, safe to administer, and could be shipped worldwide in a highly stable form (i.e. soybeans). The fact that extensive procedures for processing soybeans into human consumables already exist suggest that this work could be readily translated to the production of a plant derived, edible adjuvant useful in novel human vaccine formulations.
