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October 04, 2001


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HARVARD GAZETTE ARCHIVES

Vaccine prevents cavities:

Ready for tests on tots

By William J. Cromie
Gazette Staff

Martin Taubman and Daniel Smith
Martin Taubman (left) and Daniel Smith lead a team that has proved the safety of a vaccine to prevent dental cavities. (Staff photo by Stephanie Mitchell)

Imagine never needing to have another tooth drilled and filled. Imagine a vaccine that prevents cavities in your children's teeth for their entire lives. Furthermore, no injection would be necessary; the vaccine would simply be sprayed into people's noses.

Such a vaccine has been made and successfully tested on humans and rats by researchers at the Forsyth Institute, an affiliate of the Harvard School of Dental Medicine in Boston. Its safety has been demonstrated in young men; and rats infected with the bacteria most responsible for human tooth decay enjoyed a significant reduction in cavities.

"Things are at the point where we're ready to test it on 1-year-olds," says Daniel Smith, associate clinical professor. He and Martin Taubman, a professor of oral biology, lead the team that developed the vaccine. Their studies show that children first become infected with the major cavity-causing bacteria, called Streptococcus mutans, at 18 months to 2 years of age.

"Our goal is to eliminate or greatly reduce caries in primary teeth," Smith notes. (Dentists use the word "caries" rather than "cavities.") These "baby teeth" are later replaced by permanent teeth, so the plan would be to give kids another vaccine spray when they start school. Hopefully, that would protect them for life.

"We feel that we're working not just to address the problem of dental caries," Smith notes. "Most childhood infections involve mucous membranes in the gut or respiratory system," including diarrhea, which is a scourge in poor countries. Cells stimulated by vaccines and drugs put into mucous membranes lining the nose and rectum can migrate to other sites of infection. "Therefore, we believe our system can be used to contribute to solving these other problems," Smith says.

Billions of rotting teeth

Whether you call them caries or cavities, they make life miserable for billions of people. The World Health Organization claims that more than 50 percent of the world population of more than 6 billion are troubled by tooth decay. The Surgeon General reports that a third of poor children in the United States, ages 2 to 9, need treatment for cavities. Between 40 and 50 percent of poor blacks, 12 years and older, suffer from untreated decaying teeth.

"A caries vaccine would be a major public health measure in alleviating such devastating disease," Taubman says.

Streptococcus mutans makes a substance called glucan, which forms a scaffold to which bacteria cling. Glucan and bacteria live in a difficult-to-remove living film known as plaque. Securely anchored on plaque, S. mutans produces lactic acid as a by-product of sharing the sugar in human diets. This acid erodes the hard enamel covering that shields teeth from decay.

Nature provides some protection again these attacks. Glands within the pink, skinlike mucous membrane that lines your mouth secrete saliva as well as antibodies that fight infection. Inadequate brushing and lack of dental care causes the decay to overwhelm the antibodies.

Taubman and Smith took a close look at saliva and found specific antibodies that would make a vaccine to stimulate the body to fight tooth rot. They focused on an enzyme called GTF (glucosyltransferase), which bacteria employ to make the glucan that binds them to plaque.

Without GTF, glucan cannot form, and S. mutans cannot accumulate in numbers large enough to cause enamel to deteriorate. Make a vaccine that stimulates production of antibodies against GTF and teeth will be saved.

After many tests, the Forsyth team gave a GTF vaccine to a group of about 80 young men. Some of them swallowed a capsule containing the enzyme, others had it dripped on the inside surface of their lips, and others acted as an untreated comparison group. The main purpose of the experiment was to test for safety.

"The tests proved the safety of the vaccine, and it delayed accumulation of S. mutans in plaque for several months," Smith says.

Other kinds of vaccines

Taubman and Smith tried another form of the vaccine on rats. Instead of giving the whole GTF enzyme, they injected only parts of it into the rats. These shots protected the animals as well as did the whole enzyme.

To strengthen the protective response of such a vaccine, the research team is developing adjuvants, or boosters. Proteins from bacteria that cause cholera and food poisoning were studied for the purpose. The scientists have focused on a booster from the bacteria Escherichia coli from which toxicity has been removed. They believe that combining this booster with pieces of the GTF enzyme will stimulate production of enough antibodies to protect children and adults from S. mutans.

At this point Smith and Taubman feel that either vaccine could be safely given to children. A nasal spray would be an easy way to vaccinate most kids. However, another way to administer the drug needs to be found for those suffering from asthma and other childhood respiratory diseases. The researchers believe a suppository can do the trick, because cells stimulated by the vaccine can travel through the blood and home in on distant sites such as salivary glands.

The next step is to find the best way to package GTF or the combination vaccine. Forsyth scientists are working on this with Cambridge Scientific. One way is to put the vaccine into microparticles made of the same material used for surgical sutures that are eventually absorbed by the body. "Such packaging seems to stimulate a stronger protective effect than the enzyme alone," Smith points out.

"We're now ready to test the vaccine in humans," he continues. "But we're frustrated by a lack of money to produce it in the quantities needed." The National Institutes of Health supported the basic research, but does not provide funds for manufacturing drugs.

Meanwhile, Taubman and Smith have found another vaccine target, a protein needed by S. mutans to construct itself. Laboratory tests reveal that immunizing rats with this protein successfully protects them against cavities.

Chickens given the protein make antibodies against it, and these antibodies collect in the yolks of their eggs. "When we extract the antibodies from the yolks and give them in nose drops to rats," Smith notes, "they get the same level of protection from caries as those vaccinated with the nasal spray."









Copyright 2002 by the President and Fellows of Harvard College