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Dental Vaccines

Martin Taubman and Daniel Smith, dental immunologists at the Forsyth Dental Center, have been working on an alternate method of preventing S. mutans from colonizing children’s teeth. The researchers know that humans develop antibodies to mutans streptococci (the group of bacteria containing S. mutans) when they’re around three years old, after the bacteria have already colonized their teeth. People retain these antibodies as adults but never develop enough to completely wipe out the bacteria. The team’s goal, therefore, is to develop a vaccine that can be given to children before their mouths are colonized by S. mutans. That way, when the bacteria infect them, the antibodies would already be present.

A vaccine that Taubman and Smith have developed thus far induces the body to produce antibodies against an enzyme produced by mutans streptococci. The enzyme-glucosyltransferase, or GTF-breaks down the sugar in food into more simple sugars-glucose and fructose. The resulting simple-sugar molecule is critical because it is the substance to which bacteria bind, like dust bunnies to Velcro. Thus the enzyme helps create a mass of bacteria large enough to metabolize other carbohydrates and produce lactic acid. “You get enough bugs, you get enough acid, you produce a hole,” says Taubman.

The antibodies produced by the vaccine interfere with the site on the enzyme that cleaves the complex sugars, preventing them from being broken down into the components to which the bacteria like to adhere. The vaccine was first tested on animals, who, after immunization, developed fewer cavities. It was then given to adult humans, whose immune systems have been shown to produce antibodies.

Taubman and Smith are in the process of refining the vaccine so that it can be made artificially-that is, not from the live mutans streptococci themselves, but from molecular components-but do not immediately anticipate testing it on children simply because the Forsyth Dental Center lacks the necessary medical infrastructure. They anticipate working with centers that specialize in vaccines for children to piggyback their vaccine onto those developed for other diseases.

Researchers are also developing vaccines to help prevent periodontal disease. Scientists originally thought the task would be daunting because, unlike tooth decay, the disease appeared to involve the complex interactions between many species of bacteria: some bacteria live in the periodontal pocket-the space between the gums and the teeth-and interact with a second set that colonizes the tooth above the pocket.

But oral ecologists have recently discovered that most periodontal disease may be caused by just three bacteria. One species is responsible for most juvenile periodontia, while two other species cause most infection in adults. At the University of Washington, researchers are developing a vaccine for one of the species of bacteria, Porphyromonas gingivalis, that infects adults. The research began several years ago when Roy Page, professor of periodontics at the University of Washington School of Dentistry, created a vaccine from deactivated Porphyromonas cells that were harmless but could still initiate an immune response. He then added an adjuvant-a mix of oils and other ingredients-that helps the antigen last longer and makes the immune cells more responsive-and administered the vaccine to macaque monkeys.

Since most animals do not normally get periodontal disease-the only species it shows up in other than humans is beagles-Page wrapped threads around the bottom of the monkeys’ teeth to encourage bacteria to colonize. He then infected the monkeys with all the types of bacteria that cause periodontal disease in adult humans. After 36 weeks, he performed a computer analysis of dental x-rays taken before and after the study to measure the difference in bone destruction, the usual result of gum infection caused by Porphyromonas gingivalis. The analysis showed that a control group experienced significant bone decay while the vaccinated monkeys had virtually none. The results suggested that the antibodies developed by the monkeys against Porphyromonas were also effective against the other species of bacteria.

The U.S. Food and Drug Administration requires that vaccines be developed from specific proteins that induce an immune response, instead of from killed cells that may induce unpleasant side effects in humans. One likely candidate is a protein on the surface of Porphyromonas called cystine protease that induces an immune response to the bacteria, and seems to cause no side effects. The FDA also prefers proteins that are made from pure antigen-that is, antigen derived directly from DNA-to reduce the chance that they will contain “impurities,” or other cell components, that may cause unwanted reactions. To that end, Page is working with Marilyn Lantz, a genetics researcher at the University of Indiana, to make a recombinant version of the protein from pure DNA for further testing in monkeys. “If we get protection from cystine protease,” Page says, “we’ll ask the FDA to do clinical trials for safety in humans.”

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Tagged: Biomedicine

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