By David N. Leff
A sweet tooth is a porous tooth.
Toddlers who suck on candies and devour sugary treats are prime candidates for dental caries ¿ cavities in their molars, when these milk teeth erupt.
Research immunologist Daniel Smith explains the connection between oral sucrose and teeth full of holes: ¿Dental caries is an infectious disease. It¿s caused by the acid secretion of bacteria called mutans streptococci. These organisms infect the mouth, generally beginning around 18 months of age. And they accumulate in the oral cavity when sucrose is present.¿
Sucrose is the substrate of an enzyme, glucosyltransferase (GTF), which is constitutively synthesized by these mutans streptococci. The glucan molecules that are formed by the GTFs then provide binding sites for the mutans, as well as other microorganisms. Therefore the bacteria accumulate, and end up secreting lactic acid, which eventually erodes the tooth surface. It dissolves the calcium phosphate crystals that make up the enamel.¿
Smith, a senior staff member at the Forsyth Institute in Boston, which focuses on oral and craniofacial science, observed that lactic acid and many other common corrosive chemicals, such as vinegar, constitute a constant menace to teeth. ¿Even cola soft drinks,¿ he pointed out, ¿are acidic.
¿The classic experiment,¿ Smith recalled, ¿is to take a tooth ¿ hopefully a tooth that¿s been extracted ¿ and put it in a cola solution, where it will dissolve. You won¿t have a tooth there the next morning, because colas are acidic environments.
¿Most acids can dissolve a tooth surface,¿ he pointed out. ¿It just happens that there are a few bacteria in the oral cavity that can produce the requisite amount of acid, as well as continue to metabolize in low-acid conditions. That¿s one of the reasons why this microorganism, mutans streptococci, has become associated with the pathogenicity of tooth decay. It can produce this acid while continuing to be metabolically active at a pH of 4, which is fairly acidic for anything.¿
We Have Met The Enemy And It Is Sugar
¿Most of us ¿ not all ¿ are colonized with this bacterium by the time we reach adulthood,¿ Smith continued. ¿There are probably 400 different types of microorganisms in the oral cavity. The first infectious exposure comes between the ages of 18 and 36 months, when the primary teeth are erupting in the mouth. Apparently the mutans, while they¿ll colonize all teeth, prefer the nooks and crannies of molars over incisors. And anywhere from 50 percent to 80 percent of us become infected during that initial infectious period. But if the mutans do not find a space during that initial period, they are shut out until new, secondary, teeth erupt in the mouth, which occurs during 6 to 12 years of age. It¿s the second time in one¿s life when we have the potential of becoming infected, and most of us do.
¿What causes the problem chiefly,¿ Smith went on, ¿is when you provide lots of sucrose. The reason is that the GTF makes lots of glucan, and the bugs accumulate in the oral cavity, which is pretty acidic. If the sucrose levels are down thanks to oral hygiene, such as tooth-brushing and regular trips to the dentist, then the disease is less of a problem. And of course, fluoride in the diet strengthens the enamel surface from acid dissolution. So that¿s another tack for keeping tooth decay at bay.¿
Research immunologist Martin Taubman, head of immunology at the Forsyth Institute, is senior author of a paper in the July issue of Infection and Immunity, a journal of the American Society for Microbiology. Its title: ¿Diepitopic construct of functionally and epitopically complementary peptides enhances immunogenicity, reactivity with glucosyltransferase, and protection from dental caries.¿ Smith is the co-author.
That mouthful reports on the latest phase in Forsyth¿s program to develop an anticavity vaccine.
¿One of the key findings in this paper,¿ Smith told BioWorld Today, ¿was that we were able to show that a synthetic vaccine against dental caries ¿ which comprises two of the important functional epitopes on the glucosyltransferase molecule ¿ was effective in inducing an immune response that was protective in our animal model system. GTF,¿ he elaborated, ¿is an enzyme that synthesizes glucan and sucrose, with the ability to both synthesize the glucan and bind it. So our synthetic peptide vaccine put together epitopes from both of those regions on the same synthetic peptide. This gave an enhanced immune response, rather than immunizing with the individual epitopes themselves.
¿Two of four previous papers since 1995,¿ Smith noted, ¿had to do with enhancing the mucosal immune response to many types of antigens. Our interest, of course, is in caries vaccines. Both of those articles proposed applications for the intranasal delivery of a vaccine that we think would be most efficacious in a human system.¿
The co-authors believe that to protect against caries over the long term is to introduce an antigen-directed vaccine to children at about 1 year of age ¿ after teeth have begun to emerge, but before mutans streptococci bacteria have started to colonize their mouths. At this stage, a child¿s immune system is developed enough to produce antibodies against accumulation of the tooth-decaying mutans. Once the bacteria begin to accumulate, antibodies may no longer halt the caries process.
A Child-Friendly Squirt Up The Nose
Their current focus is on a ¿mucosal¿ vaccine that can be squirted into the nostrils, adjacent to the target oral cavity.
In a series of preclinical in vivo experiments, the co-authors injected four variants of their vaccine ¿ GTF, glucan, catalytic and glu-cat combined ¿ into 54 female rats. The test included two sham rodent cohorts, one harboring streptococci bacteria in their mouths, all the others initially free of the pathogen. Then, 62 days after vaccination, plus repeated challenges with carigenic bacteria, 100 percent of the untreated sham rats had contracted caries, compared with 30 percent for strep-sterile shams. So were an equal number of glu-cat combined-epitope vaccines. Half of the GTF recipients were protected.
¿We have already had this intact GTF peptide in Phase I clinical trials in adults,¿ Smith observed, ¿with an FDA IND. What we now need to do is vaccinate 1- to 2-year-old children, because they¿re not yet infected. We are hoping that FDA will grant us an addendum for that IND, to put it in the pediatric population. Then we¿ll go into clinical trials.¿