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Vaccines for the 21st Century: A Tool for Decisionmaking
Several companies have expressed interest in becoming partners for further development and preparation for human trials.
Despite tremendous pressure, Group A streptococcus has not developed antibiotic resistance. Penicillin is still effective in treatment and in prophylaxis.
There is sometimes a fine line between immunizing epitopes and tissue-crossreactive epitopes. Researchers hope to clarify this issue when the final vaccine construct is tested in animals, especially primates whose immune response genes are most similar to humans.
Recent developments indicate that it may soon be possible to use vaccines not only prophylactically, to protect against infection and reinfection with Helicobacter pylori (HP), but also therapeutically, using active immunization to clear existing infection and prevent reinfection.
Incidence and Burden. HP is the cause of the vast majority of cases of peptic ulcer, over 90 percent of duodenal ulcers, and perhaps 80 percent of gastric ulcers. Once infected with HP, the lifetime risk of acquiring peptic ulcer disease is about 20 percent, with additional cases of atrophy. The risk of gastric cancer is also significant: overall, the lifetime risk of gastric cancer in the United States is about 1 percent, and 60 percent of these cases are attributable to HP.
The association with cancer is even more important elsewhere in the world. In the United States, seroprevalence is about 50 percent by age 50; in developing countries it approaches 100 percent and the infection is acquired earlier, often in childhood. Early acquisition and decades of chronic inflammation appear to be important in the genesis of gastric cancer. The World Health Organization has classified HP as a definite carcinogen.
Pathobiology. HP is a Gram-negative bacterium that is transmitted by saliva and vomitus; young children are the most active transmitters. Once ingested, the bacterium is well-adapted to penetrate the mucous lining of the stomach and colonize the gastric epithelium. It has a spiral shape designed for boring through this viscous environment, and a polar flagella that provides motility and also plays a role in virulence. HP does not invade the host; instead, it causes an “offshore” or surface infection of the epithelium and sometimes penetrates into the gastric glands. Once established, it is a lifelong persistent infection that is not cleared by host immune response.
The result of chronic infection is inflammation of the gastric epithelium leading ultimately to atrophy and destruction of the gastric glands, lymphoid follicles, and a massive accumulation of T and B cells. Secondary effects of