Helicobacter pylori, bacterial perpetrator of peptic ulcer and gastric cancer, colonizes the stomachs of more than half the world's human population "H. pylori is the second most common bacterial infection in man," observed microbiologist Thomas Boren at Ume University in Sweden." (Only tooth-invading Streptococcus mutans is more prevalent.)

"Scientists believe the ulcer infection starts in infancy and lasts for decades - perhaps for a lifetime," Boren noted. "In the U.S. and Europe, 30 percent of the population is infected by H. pylori, as are 70 percent worldwide. And about 1 percent will die of stomach cancer, which is among the commonest malignancies in the world."

Peptic ulcer disease affects 25 million Americans, and 500,000 to 850,000 new cases are diagnosed annually in the U.S. The American Cancer Society estimated 22,600 new stomach cancer patients in 1998 and 13,700 deaths - 40 percent to 60 percent of them related to H. pylori infection. Stomach cancer is the leading cause of death in China and Japan.

In the 1930s, gastric carcinoma was the leading cause of death among men in the U.S. Its connection to gastric and intestinal ulcers was unclear. Today it ranks eighth. Until the 1980s, people with stomach ulcers were condemned to a stress-free lifetime of bland, non-spicy food - alcohol, caffeine and nicotine forbidden - bed rest, sedatives, tranquilizers, antacids and psychotherapy.

Bacteriologists discovered Helicobacter pylori circa 1983-85. Soon thereafter, one of them, an Australian hospital resident named Barry Marshall, deliberately swallowed a culture containing a billion of the organisms. He woke feeling hungry and irritable, with a headache, bad breath and gastritis - stomach inflammation. Two weeks later he was asymptomatic. Marshall claimed H. pylori to be the true cause of gastric ulcers.

Currently, the only therapy against the stomach-ravaging bacterium is an antacid combined with antibiotics - to which the wised-up pathogen is becoming resistant. The deep purple acid-suppressing capsule is Prilosec (AstraZeneca), the highest-selling prescription drug in the world. (See BioWorld Today, Jan. 14, 1999, p.1.)

Binational Academics Team Up Against Common Foe

Foreseeing the eventual drug-resistant eclipse of antibiotics, Sweden's Thomas Boren is concentrating on long-term development of a vaccine to immunize susceptible people against H. pylori. He is senior author of a research paper in the current Science, dated July 26, 2002. Its title: "Helicobacter pylori SabA adhesin in persistent infection and chronic inflammation." His leading co-author is molecular microbiologist Douglas Berg at the Washington University School of Medicine in St. Louis.

"These findings should improve our understanding of how H. pylori infection happens," Berg told BioWorld Today, "how our immune system responds to it, and how the bacteria cope with that response. We also hope that understanding how their adhesion proteins work will lead to a vaccine against H. pylori infections and to new drugs for treating or diminishing their severity."

"Overall," Boren said, "our study suggests a dynamic and constantly evolving relationship between bacteria and host. Of the millions of H. pylori that live in an infected person's stomach, we and our collaborators believe some reside for a time close to stomach cells, while others stay a short distance away in the film of mucus that protects cells from the secreted acids in the stomach cavity. The bacterial population," he continued, "thereby achieves a beneficial trade-off. In any given patch of stomach tissue, bacteria sitting close to stomach cells are well nourished but at higher risk of attack by the body's prowling immune cells.

"A spoonful of sugar may make the medicine go down," Boren went on, "but for the 50 percent of the global population whose stomachs contain the H. pylori bacterium, other sugars have less sweet implications. Certain glycoproteins in the body," he explained, "meant to help the immune system fight the infection, actually make it worse. These findings help explain why H. pylori is such a tenacious, virulent bug, and provide new prospects for making a vaccine against it.

"The bacteria's ancestor seems to have come up with its adherent proteins all by itself," Boren suggested. "This uniqueness bodes well for a vaccine cocktail' of adhesin proteins. My team and others," he recounted, had previously identified another adhesin protein called BabA' on the bacterium's surface, that binds to the sugar molecule Leb.' To investigate whether H. pylori used other adhesions for similar purposes, we generated a mutant form of the bacteria lacking the BabA. And we named the sugar to which it bound the sdiLex' gene.

"Using biopsies from human patients and a rhesus monkey," Boren recounted, "we found that the mutant bacteria were binding to mucus membrane cells of infected individuals, and not those of healthy people. The membrane cells seemed to be shooting themselves in the foot, so to speak, by displaying more glycoproteins once they were under siege by H. pylori. Aided by the sequenced bacterial genome, we identified the gene encoding its adhesin protein. We named it SabA,' for Sialic acid binding adhesin."

Unique Proteins = Ideal Vaccine Candidates

Boren continued: "The attachment adhesions we have identified, BabA and SabA, are proteins absolutely unique for Helicobacter pylori. Thus, these molecules are prime candidates for a vaccine specific to Helicobacter. This is especially important in the gastrointestinal tract, where many beneficial bacteria make up a balanced environment.

"For use as vaccines," he pointed out, "the adhesins will be prepared as recombinant proteins by molecular biology techniques, and supplied to the patient most likely in a drinkable form, similar to the cholera vaccine. The vaccine will then trigger the recipient's immune system to make antibodies and activate its responses that target the adhesin protein. As H. pylori infection is transmitted within families, from parents to children, thus a therapeutic vaccine would break this route of transmission. Unfortunately, it would not be useful for patients with stomach cancer.

"Later on," Boren suggested "especially in the developing world, I would imagine a prophylactic vaccine, administered to symptomatic patients to eradicate or quench the infection. However," he noted, "I believe it would be wise to continue to treat patients with overt disease, such as peptic ulcer, with antibiotics, to eradicate infection, preferably in combination with a vaccine. We are talking six to eight years," Boren concluded, "before our vaccine is available for patients."