Let Your Antibody Work Immunize Early 1. L. SHKLAIR and H. J. KEENE Naval Dental Research Institute, Naval Base, Building l-H, Great Lakes, Illinois 60088, USA
It is hopeful that some day a vaccine may be useful in the prevention or control or both of dental decay in human populations. The methods proposed to date have theorized that antibodies could control Streptococcus mutans in the mouth by one or more of the following methods: (1) destroying the organism by some lytic process, (2) interfering with the metabolism of the organism, or (3) preventing their adherence to tooth surfaces. This latter approach, the interference with the mechanism that causes attachment of the organism to teeth by anti-glucosyltransferase antibody, appears to be the approach favored at this time. Since the immune response depends on antibody secreted into saliva, a significant amount of specific antibody will have to be available to be effective. In well-established infections where the organisms are already well entrenched in the posterior interproximal spaces and the pits and fissures of the occlusal surfaces, it may be asking a great deal of salivary antibody to control the infection. It would appear to be more reasonable to administer the vaccine or bacterin before the initial colonization of S mutans on the teeth, rather than after the colonization has already taken place. One question that has concerned us in our immunization studies is, "when is the most effective time to immunize"? The results of two studies reported by our laboratory last year strongly indicated that animals and eventually humans might benefit most from immunization if the procedure is started very early in life, either before or during the early stages of deciduous tooth eruption. The studies supporting this idea dealt with the initial acquisition and natural history of S mutans infection in monkeys and young children. In the monkey experiment, six pregnant
Macaca fascicularis monkeys were infected with S mutans. Shortly after birth (3 to 11 weeks), their offspring were either intraorally immunized with a Formalin-killed whole cell suspension of S mutans or sham immunized with S salivarius. Although transmission of S mutans took place in both groups of baby monkeys, there was a definite trend indicating that the S mutans-immunized group acquired fewer of the organism from their mothers than the shamimmunized group. There were also fewer tooth surface sites in the mouth that harbored the organism in the immunized group than in the sham group. These results closely parallel those of Evans, Emmings, and Genco3 who have shown that immunized Macaca fascicularis monkeys have fewer S mutans in their plaque and many fewer sites in their dentition infected with S mutans as compared to sham-immunized control monkeys. In the second experiment,2 we were interested in learning at what age children first become infected with S mutans and the site or sites most frequently colonized. In human infants without teeth, S mutans could not be isolated from samples taken by rubbing a cotton swab over the oral mucous membranes. Children having no more than erupted central and lateral incisors also did not harbor the organism. When all the primary teeth were erupted, but no interproximal molar contacts were present, 37% of the children sampled were found to be carriers of S mutans. The highest frequency of isolation, 52%,, occurred in children whose posterior interproximal surfaces were in contact with each other. This site between contacting first and second deciduous molars appears to be the primary site of colonization in young children. These two briefly summarized studies may
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Vol 5S 1976
IMMUNIZE EARLY
serve to provide some preliminary guideline for the development of an immunization schedule, whether it be in humans or in animal model systems. Although it has recently become possible to demonstrate antibody levels against S mutans4-6 and its metabolic products in serum or saliva or both, the results reported as to the protective effects of immunization have been varied and contradictory. For antibody to be most effective, the available evidence suggests that immunization should be given before the primary teeth fully erupt into the mouth, and before the tooth surfaces become available for colonization by S mutans. It seems plausible that it might be easier for the antibody to prevent infection and colonization of the teeth rather than to control the infection once it is already established. Once the organisms have colonized the teeth, particularly the interproximal spaces and occlusal surfaces, it would appear that it is asking much of the antibody to control the infection. Give your antibody a break-let it work to keep the organism out of the mouth rather than fight an established infection.
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References 1. EDMAN, D.C.; SHKLAIR, I.L.; KEENE, H.J.; and CATALANOTrO, F.A.: Attempted Interference with Intrafamily Transmission of Streptococcus mutans in Monkeys, J Dent Res 53 (Special Issue): Abstract No. 866, 1974. 2. CATALANOTTO, F.A.; SHKLAIR, I.L.; and KEENE,
H.J.: Prevalence and Localization of Streptococcus mutans in Infants and Children, JADA 91: 606-609, 1975. 3. EVANS, R.T.; EMMINGS, F.G.; and GENCO, R.J.: Salivary IgA Antibodies Which Inhibit Implantation of S mutans on M irus Tooth Surfaces Show Specificity for Immunizing Strain, Infect Immum 12: 293-302, 1975. 4. HAYASHI, J.A.; SHKLAIR, I.L.; and BAHN, A.N.: Immunization with Dextransucrases and Glycosidic Hydrolases, J Dent Res 51: 422-436, 1972. 5. GENcO, R.J.; EVANs, R.T.; and TAUBMAN, M.A.: Specificity of Antibodies to Streptococcus mutans; Significance in Inhibition of Adherence in MESTECKY, J., and LAWTON, A.R. (eds): The Immunoglobulin A System, New York: Plenum Press, 1974, pp 327-336. 6. CHALLACOMBE, S.J.; GUGGENHEIM, B.; and LEHNER, T.: Antibodies to an Extract of Streptococcus mutans, Containing Glucosyltransferase Activity, Related to Dental Caries in Man, Arch Oral Biol 18: 657-668, 1973.
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It is hopeful that some day a vaccine may be useful in the prevention or control or both of dental decay in human populations. The methods proposed to date have theorized that antibodies could control Streptococcus mutans in the mouth by one or more of the following methods: (1) destroying the organism by some lytic process, (2) interfering with the metabolism of the organism, or (3) preventing their adherence to tooth surfaces. This latter approach, the interference with the mechanism that causes attachment of the organism to teeth by anti-glucosyltransferase antibody, appears to be the approach favored at this time. Since the immune response depends on antibody secreted into saliva, a significant amount of specific antibody will have to be available to be effective. In well-established infections where the organisms are already well entrenched in the posterior interproximal spaces and the pits and fissures of the occlusal surfaces, it may be asking a great deal of salivary antibody to control the infection. It would appear to be more reasonable to administer the vaccine or bacterin before the initial colonization of S mutans on the teeth, rather than after the colonization has already taken place. One question that has concerned us in our immunization studies is, "when is the most effective time to immunize"? The results of two studies reported by our laboratory last year strongly indicated that animals and eventually humans might benefit most from immunization if the procedure is started very early in life, either before or during the early stages of deciduous tooth eruption. The studies supporting this idea dealt with the initial acquisition and natural history of S mutans infection in monkeys and young children. In the monkey experiment, six pregnant
Macaca fascicularis monkeys were infected with S mutans. Shortly after birth (3 to 11 weeks), their offspring were either intraorally immunized with a Formalin-killed whole cell suspension of S mutans or sham immunized with S salivarius. Although transmission of S mutans took place in both groups of baby monkeys, there was a definite trend indicating that the S mutans-immunized group acquired fewer of the organism from their mothers than the shamimmunized group. There were also fewer tooth surface sites in the mouth that harbored the organism in the immunized group than in the sham group. These results closely parallel those of Evans, Emmings, and Genco3 who have shown that immunized Macaca fascicularis monkeys have fewer S mutans in their plaque and many fewer sites in their dentition infected with S mutans as compared to sham-immunized control monkeys. In the second experiment,2 we were interested in learning at what age children first become infected with S mutans and the site or sites most frequently colonized. In human infants without teeth, S mutans could not be isolated from samples taken by rubbing a cotton swab over the oral mucous membranes. Children having no more than erupted central and lateral incisors also did not harbor the organism. When all the primary teeth were erupted, but no interproximal molar contacts were present, 37% of the children sampled were found to be carriers of S mutans. The highest frequency of isolation, 52%,, occurred in children whose posterior interproximal surfaces were in contact with each other. This site between contacting first and second deciduous molars appears to be the primary site of colonization in young children. These two briefly summarized studies may
C224 Downloaded from jdr.sagepub.com by guest on July 26, 2015 For personal use only. No other uses without permission.
Vol 5S 1976
IMMUNIZE EARLY
serve to provide some preliminary guideline for the development of an immunization schedule, whether it be in humans or in animal model systems. Although it has recently become possible to demonstrate antibody levels against S mutans4-6 and its metabolic products in serum or saliva or both, the results reported as to the protective effects of immunization have been varied and contradictory. For antibody to be most effective, the available evidence suggests that immunization should be given before the primary teeth fully erupt into the mouth, and before the tooth surfaces become available for colonization by S mutans. It seems plausible that it might be easier for the antibody to prevent infection and colonization of the teeth rather than to control the infection once it is already established. Once the organisms have colonized the teeth, particularly the interproximal spaces and occlusal surfaces, it would appear that it is asking much of the antibody to control the infection. Give your antibody a break-let it work to keep the organism out of the mouth rather than fight an established infection.
C225
References 1. EDMAN, D.C.; SHKLAIR, I.L.; KEENE, H.J.; and CATALANOTrO, F.A.: Attempted Interference with Intrafamily Transmission of Streptococcus mutans in Monkeys, J Dent Res 53 (Special Issue): Abstract No. 866, 1974. 2. CATALANOTTO, F.A.; SHKLAIR, I.L.; and KEENE,
H.J.: Prevalence and Localization of Streptococcus mutans in Infants and Children, JADA 91: 606-609, 1975. 3. EVANS, R.T.; EMMINGS, F.G.; and GENCO, R.J.: Salivary IgA Antibodies Which Inhibit Implantation of S mutans on M irus Tooth Surfaces Show Specificity for Immunizing Strain, Infect Immum 12: 293-302, 1975. 4. HAYASHI, J.A.; SHKLAIR, I.L.; and BAHN, A.N.: Immunization with Dextransucrases and Glycosidic Hydrolases, J Dent Res 51: 422-436, 1972. 5. GENcO, R.J.; EVANs, R.T.; and TAUBMAN, M.A.: Specificity of Antibodies to Streptococcus mutans; Significance in Inhibition of Adherence in MESTECKY, J., and LAWTON, A.R. (eds): The Immunoglobulin A System, New York: Plenum Press, 1974, pp 327-336. 6. CHALLACOMBE, S.J.; GUGGENHEIM, B.; and LEHNER, T.: Antibodies to an Extract of Streptococcus mutans, Containing Glucosyltransferase Activity, Related to Dental Caries in Man, Arch Oral Biol 18: 657-668, 1973.
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