Do you remember going to the dentist to get a cavity filled? No matter how kindly and skillful your dentist, getting a filling is not fun. Beyond discomfort, there is also a cost in both time and money. Cavities are also called dental caries, and we will be using that more technical name in this month’s story.

Caries are a widespread problem throughout the United States. By the age of 40, about 98% of Americans have had dental caries (Nash and Taubman, 2006). And one-fourth of Americans suffer from missing teeth or even endentulism as a result of dental caries. Untreated dental caries can lead to a host of oral health and overall health problems, including heart disease.

Dental caries is an infectious disease caused by bacteria in the mouth. What you eat and how you care for your teeth play a role, too.

Every child is born with a sterile mouth, but between 18 and 36 months of age, the mouth is colonized by a variety of bacteria, most notably the bacteria called mutans streptococci. This is the main culprit in forming caries.

Like all bacteria, the mutans streptococci bacteria are little living things, so they need food. Guess what their preferred food is: that’s right it’s sugar. In particular, it’s the sugar called sucrose, the kind of everyday sugar you get in little packets and sugar bowls. Mutans streptococci and sugar act together to makes acids that attack the teeth.
Here are the steps:

1.		Mutans streptococci produce an adhesive (sticky) molecule, called adhesin, which allows the bacteria to attach to the film on teeth. Mutans streptococci bacteria that stick to the teeth and the presence of sucrose lead to dental caries.
2.		Mutans streptococci also produce other enzymes called glucosyltransferases. Caries form only when these enzymes and sucrose are present.
3.		The glucosyltransferases break down sucrose into its components, simple sugars known as fructose and glucose.
4.		Mutans streptococci use these sugars to make new molecules, called glucans.
5.		Glucans interact with glucan binding proteins and glucosyltransferases on the surface of the mutans streptococci bacteria.
6.		Glucans and the bacteria accumulate on the teeth and are known as dental plaque. In other words, dental plaque can consist of large amounts of mutans streptococci.
7.		When large amounts of plaque form on teeth and when sugars are present to feed the bacteria, mutans streptococci produce lactic acid. The acid makes holes in the teeth, and causing dental caries.

Could We Really Have an Anti-Cavity Vaccine?

In order to make a vaccine to prevent dental caries, it was first necessary to completely understand the mechanism explained above. Detailing this process of dental caries formation was spearheaded by Dr. Martin Taubman, his colleague Dr. Daniel Smith and a team of researchers at The Forsyth Dental Institute in Boston.

Most of us don’t think of protecting our teeth with a vaccine, but Drs. Taubman and Smith found that the immune system can be used to respond to dental caries. They have been working for over 30 years to develop a vaccine for dental caries.

Here’s how the immune system defends the body against foreign invaders (called antigens ): The immune system recognizes, attacks, destroys and eliminates the invader from the body. Specifically, the immune system activates cells to make antibodies against the antigen. Each antibody has a fingerprint that matches a specific antigen. When an antibody encounters its matching antigen, the antigen is "caught" and destroyed.

A vaccine is a version of the antigen introduced into the body on purpose … it is meant to stimulate the creation of antibodies and protect the person when the real invader arrives.

So, why not try to create a vaccine for mutans streptococci bacteria, which is not present when babies are born, but arrives later, as an invader?

Drs. Taubman and Smith and began this research in vitro by stimulating mutans streptococci to make artificial biofilm (plaque). When sucrose was added, plaque developed. However, Drs. Taubman and Smith found they could control the amount of plaque by incubating the bacteria with sucrose and an antibody to the enzyme glucosyltransferase. To repeat this experiment in animals, these researchers had to identify an antigen that could be used to combat the disease.

They used a piece of the enzyme glucosyltransferase, or a piece of the enzyme as an antigen. They injected this antigen near the salivary glands of rats to see if the rats would produce an immune response. The immunized rats produced the antibody, immunoglobulin A (IgA) in their saliva and had fewer dental caries. This led Drs. Taubman and Smith and their team to hypothesize that glucosyltransferase could be an effective vaccine for the reduction of dental caries.

To test this hypothesis, twenty-five college students volunteered either to be immunized with glucosyltransferase or to be in the control group. Before beginning the experiments the researchers cleaned the teeth of all of the subjects to minimize the amount of mutans streptococci present in the mouth. Then they administered the vaccine by mouth. “The results showed elevation in antibody and a significant reduction in the recolonization of the teeth with mutans streptococci,” said Dr. Taubman, “but this only lasted for up to 42 days. After 42 days the results from the experimental group were the same as the control group.” The researchers concluded that, while the vaccine reduced the amount of bacteria temporarily, adults were not the right target population for the vaccine.

Researchers believe that the vaccine would work best if administered before initial bacterial colonization. Because mutans streptococci colonize the baby’s mouth between 18 and 36 months of age, the correct target population would be children from 12 to 24 months who have a functioning mucosal (IgA) immune system.

Since children are the target population, Drs. Taubman and Smith want to make a vaccine that is really easy to administer. They are currently developing a way to passively immunize children by putting the antibody IgA or another antibody, IgG directly on children’s teeth or in their mouths before the bacteria move in. Drs. Taubman and Smith hope that this will enable the antibody to interfere with the colonization and accumulation of mutans streptococci.

Dr. Taubman believes that a vaccine against dental caries is vital. In 2004, it was estimated that 5% of the total health care budget for the United States was used for preventable dental care. That would amount to billions of dollars.

Recently, around 20% of US army reservists could not be deployed to Iraq due to teeth problems. Worldwide, five billion people suffer form tooth decay. In some areas of Europe, the rate of endentualism is as high as 78% for people over 65 years of age. “A vaccine,” says Dr. Taubman, “could reach many more people and at a much lower cost than toothbrush, toothpaste, and fluoride or dental fillings.”

He is hopeful that a vaccine will one day be available one day. But for now, “keep brushing,” he says. “And flossing couldn’t hurt.”

Dr. Martin Taubman is a dentist and immunobiologist at The Forsyth Dental Institute in Boston and a Professor of Developmental Biology at Harvard School of Dental Medicine in Boston.

To Learn More:

• Taubman M and Nash D. The scientific and public-health imperative for a vaccine against dental caries. Nature Reviews Immunology. 6: 555-563, 2006. Many of the statistics cited in this month’s story are from this article.
  
• World Health Organization. World Oral Health Report

• US Department of Health and Human Services Oral Health in America:
  A Report of the Surgeon General

About Dental Caries and Caring for Your Teeth:

• The Dental Health Foundation
  
• The British Dental Health Foundation

• American Dental Association Tooth Decay
  
• Medical Encyclopedia: Dental Cavities

Written by Rebecca Kranz with Andrea R. Gwosdow, PhD
Gwosdow Associates

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