42003:

Plants and Human Health; Delivery of Vaccines via Food Engineering.

Authors:	Arntzen, Charles, A.(A)
Affiliations:	(A): Boyce Thompson Institute for Plant Research, Inc.
Presenter:	Arntzen, Charles A., cja7@cornell.edu

Plant-derived edible vaccines are based on genes from human pathogens introduced into transgenic plants, resulting in the plant producing proteins that mimic subunits of the pathogenic organism. The resulting plant material, when provided to mice as food, acted as an oral vaccine. Approval from the FDA to test two such "edible vaccines" in human clinical trials was obtained and work is now in progress with international agencies to introduce the concept of plant-based vaccine production to developing countries that urgently need less costly vaccines to prevent infectious diseases. This system is based on mucosal immunity which is important for resistance to infections of cells lining the gut, respiratory, and genito-urinary tracts and is best achieved by delivery of vaccines at mucosal surfaces. The digestive process may sometimes limit the amount of orally delivered vaccine that reaches the gut immune system; thus vaccine adjuvants may be needed to enhance the immunogenicity of orally delivered antigens. Bacterial enterotoxins like E. coli heat-labile toxin (LT) are strong mucosal adjuvants, but they cause diarrhea and thus are unsuitable for use in humans. Mutated forms of LT (mLT) show greatly lowered toxicity but retain adjuvant activity. Thus mLT is produced in plants to increase the potency of co-expressed, orally delivered vaccines made from plants. LT is a multi-subunit protein complex assembled from one A subunit and five B subunits. The nontoxic LT-B pentamer targets LT to mucosal cells via its specific binding to the cell surfaces. Transgenic LT-B potatoes were used for the first human trial of a plan edible vaccine, and a trial with virus-like particles comprised of the capsid protein of Norwalk Virus (causal agent of severe gastroenteritis) are now underway. (This research report summarizes studies conducted with a number of colleagues, including Drs. Hugh Mason, Liz Richter, Mary Estes, John Clements, Yasmin Thanavalla, Carol Tacket, and Myron Levine. The work has been supported by the Thrasher Fund, NIH, NSF, USDA, WHO and the Rockefeller Foundation.)