CONSIDERATION of one of the challenges detailed here--the risk of inducing oral tolerance--has led my group and others to pursue edible vaccines as tools for quashing autoimmunity. Although oral delivery of antigens derived from infectious agents often stimulates the immune system, oral delivery of "autoantigens" (proteins derived from uninfected tissue in a treated individual) can suppress immune activity--a phenomenon seen frequently in test animals. No one fully understands the reasons for this difference.
Some of the evidence that ingesting autoantigens, or "self-antigens," might suppress autoimmunity comes from studies of type I diabetes, which results from autoimmune destruction of the insulin-producing cells (beta cells) of the pancreas. This destruction progresses silently for a time. Eventually, though, the loss of beta cells leads to a drastic shortage of insulin, a hormone needed to help cells take up sugar from the blood for energy. The loss results in high blood sugar levels. Insulin injections help to control diabetes, but they are by no means a cure; diabetics face an elevated risk of severe neurological and vascular complications.
In the past 20 years, investigators have identified several beta cell proteins that can elicit autoimmunity in people predisposed to type I diabetes. The main culprits, however, are insulin and a protein called GAD (glutamic acid decarboxylase). Researchers have also made progress in detecting when diabetes is "brewing." The next step, then, is to find ways of stopping the underground process before any symptoms arise.
To that end, my colleagues and I have developed plant-based diabetes vaccines, such as potatoes containing insulin or GAD linked to the nontoxic immunostimulating B subunit of the V. cholerae toxin (to enhance uptake of the antigens by M cells and processing by dendritic cells). Feeding of the vaccines to a mouse strain that becomes diabetic helped to suppress the immune attack and to prevent or delay the onset of high blood sugar.
Transgenic plants cannot yet produce the amounts of self-antigens that would be needed for a viable vaccine against human diabetes or other autoimmune diseases. But, as is true for infectious diseases, investigators are engineering chloroplasts to overcome this challenge.
Edible vaccines for combating autoimmunity and infectious diseases are close to being ready for large-scale testing in people. The technical obstacles seem surmountable. Nothing would be more satisfying than to protect the health of many millions of now defenseless children around the globe.
WILLIAM H. R. LANGRIDGE, a leader in the effort to develop edible vaccines for infectious and autoimmune diseases, is a professor in the department of biochemistry and at the Center for Health Disparities and Molecular Medicine at the Loma Linda University School of Medicine. After receiving his Ph.D. in biochemistry from the University of Massachusetts at Amherst in 1973, he conducted genetic research on insect viruses and plants at the Boyce Thompson Institute for Plant Research at Cornell University. In 1987 he moved to the Plant Biotechnology Center of the University of Alberta in Edmonton, and he joined Loma Linda in 1993.