On detecting the presence of a foreign organism in a vaccine, the immune system behaves as if the body were under attack by a fully potent antagonist. It mobilizes its various forces to root out and destroy the apparent invader--targeting the campaign to specific antigens (proteins recognized as foreign). The acute response soon abates, but it leaves behind sentries, known as "memory" T and B cells, that remain on alert, ready to unleash whole armies of defenders if the real pathogen ever finds its way into the body. Some vaccines provide lifelong protection; others (such as those for cholera and tetanus) must be readministered periodically.
Classic vaccines pose a small but troubling risk that the vaccine microorganisms will somehow spring back to life, causing the diseases they were meant to forestall. For that reason, vaccine makers today favor so-called subunit preparations, composed primarily of antigenic proteins divorced from a pathogen's genes. On their own, the proteins have no way of establishing an infection. Subunit vaccines, however, are expensive, in part because they are produced in cultures of bacteria or animal cells and have to be purified out; they also need to be refrigerated.
Plant-based vaccines are like subunit preparations in that they are engineered to contain antigens but bear no genes that would enable whole pathogens to form. Fifteen years ago Arntzen understood that edible vaccines would therefore be as safe as subunit preparations while sidestepping their costs and demands for purification and refrigeration. But before he and others could study the effects of food vaccines in people, they had to obtain positive answers to a number of questions. Would plants engineered to carry antigen genes produce functional copies of the specified proteins? When the food plants were fed to test animals, would the antigens be degraded in the stomach before having a chance to act? (Typical subunit vaccines have to be delivered by injection precisely because of such degradation.) If the antigens did survive, would they, in fact, attract the immune system's attention? And would the response be strong enough to defend the animals against infection?
Additionally, researchers wanted to know whether edible vaccines would elicit what is known as mucosal immunity. Many pathogens enter the body through the nose, mouth or other openings. Hence, the first defenses they encounter are those in the mucous membranes that line the airways, the digestive tract and the reproductive tract; these membranes constitute the biggest pathogen-deterring surface in the body. When the mucosal immune response is effective, it generates molecules known as secretory antibodies that dash into the cavities of those passageways, neutralizing any pathogens they find. An effective reaction also activates a systemic response, in which circulating cells of the immune system help to destroy invaders at distant sites.
Injected vaccines initially bypass mucous membranes and typically do a poor job of stimulating mucosal immune responses. But edible vaccines come into contact with the lining of the digestive tract. In theory, then, they would activate both mucosal and systemic immunity. That dual effect should, in turn, help improve protection against many dangerous microorganisms, including the kinds that cause diarrhea.
Those of us attempting to develop plant-based vaccines place a high priority on combating diarrhea. Together the main causes--the Norwalk virus, rotavirus, Vibrio cholerae (the cause of cholera) and enterotoxigenic Escherichia coli (a toxin-producing source of "traveler's diarrhea")--account for some three million infant deaths a year, mainly in developing nations. These pathogens disrupt cells of the small intestine in ways that cause water to flow from the blood and tissues into the intestine. The resulting dehydration may be combated by delivering an intravenous solution of electrolytes, but it often turns deadly when rehydration therapy is not an option. No vaccine practical for wide distribution in the developing nations is yet available to prevent these ills.