Published in Probe Volume 5(1): February-March 1995
Mary E. Blake, Coordinator of Clinical Research Programs
Clayton Foundation for Research
Charles J. Arntzen, Professor
Alkek Institute of Biosciences and Technology
Texas A&M University
Vaccines are primary tools in programs for health intervention for both humans and animals. They would be more widely used--especially in developing countries--if their cost of production could be reduced and if they could be distributed without refrigeration. Research underway is dedicated to solving these limitations by finding ways to produce oral (edible) vaccines in transgenic plants.
Hepatitis B virus (HBV) infection is probably the single most important cause of persistent viremia in humans. The disease is characterized by acute and chronic hepatitis, which can also initiate hepatocellular carcinoma. The prevalence of this disease in developing countries justified initial efforts to express HBV candidate vaccines in plants.
Currently, two forms of HBV vaccines are available, both of which are injectable and expensive: one purified from the serum of infected individuals and the other a recombinant antigen expressed and purified from yeast. We have transformed plants with the gene encoding the hepatitis B surface antigen (HBsAg); this is the same antigen used in the commercial yeast-derived vaccine. An antigenic spherical particle was recovered from these plants which is analogous to the recombinant hepatitis surface antigen (rHBsAg) derived from yeast. Parenteral immunization of mice with the plant-derived material has demonstrated that it retains both B- and T-cell epitopes, as compared to the commercial vaccine.
Diarrheal disease causes up to 10 million deaths per year in the developing world, primarily among children. Relatively little research on vaccines to prevent these diseases is underway, as they represent more of a nuisance than a severe problem in developed countries. Studies supported by the World Health Organization have demonstrated an effective vaccine for cholera, which provides cross-protection against enterotoxic Escherichia coli. This vaccine is not available, however, in large part due to cost of production of the bacterial toxin protein which is a component of its formulation.
To address this limitation, plants were transformed with the gene encoding the B subunit of the E. coli heat labile enterotoxin (LT-B). Transgenic potatoes expressing LT-B were found to induce both serum and secretory antibodies when fed to mice; these antibodies were protective in bacterial toxin assays in vitro. This is the first "proof of concept" for the edible vaccine.
The selection of a plant system for delivery of edible vaccines for humans has been addressed. Recognizing that it is necessary to express the desired protein in a food that is consumed raw (to avoid denaturation of the candidate vaccine protein), a system to transform banana plants has been developed. Bananas are produced in most developing countries, and are fed uncooked to infants and adults. The expression of candidate vaccines in banana fruit will be dependent upon identification of suitable tissue-specific promoters to drive the desired gene expression. Research to find these genetic regulatory elements is now underway.
Edible vaccine research is currently directed at human diseases, with a special emphasis on the developing world. The technology will also have immediate value for the production of inexpensive vaccines as feed additives for agricultural animals. Since various plant tissues are fed to animals, other plants such as alfalfa, maize and wheat could be valuable vehicles to deliver vaccines (and perhaps other pharmaceuticals) for the betterment of animal health.
(Charles Arntzen's research on vaccine development is supported in part by grants from the Thrasher Foundation, the USDA Competitive Grants Program, and the National Institutes of Health (NIH). Mary Blake's is supported by the Clayton Foundation for Research.)
Charles J. Arntzen, Ph.D.
Professor of Biochemistry and Biophysics
Plant Biotechnology Program
Texas A&M University
Institute of Biosciences and Technology
2121 Holcombe Boulevard
Houston, Texas 77030-3303
Phone: (713) 677-7601 Fax: (713) 677-7641