Secretory Immunity Following Mutans Streptococcal Infection or Immunization

  • D. J. Smith
  • R. O. Mattos-Graner
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 319)


Salivary IgA antibody responses to mutans streptococci can be observed in early childhood, sometimes even before permanent colonization of the oral biofilm occurs. Many of these early immune responses are directed to components thought to be essential for establishment and emergence of mutans streptococci in the oral biofilm. Initial responses are likely to be modulated by antigen dose, by immunological maturity, and by previous encounters with similar antigenic epitopes in the pioneer commensal flora. Our understanding of these modulating factors is modest and is an opportunity for continued investigation. Under controlled conditions of infection, experimental vaccine approaches have repeatedly shown that infection and disease can be modified in the presence of elevated levels of antibody in the oral cavity. Protection can be observed regardless of antibody isotype or method used to actively or passively provide the immune reagent. Limited clinical trials have supported the utility of both of these approaches in humans. Refinements in antigen formulation, delivery vehicles, enhancing agents and routes of application, coupled with approaches that are timed to intercept most vulnerable periods of infection of primary and permanent dentition may well provide the healthcare practitioner with an additional tool to maintain oral health.


Dental Caries Mutans Streptococcus Gingival Crevicular Fluid Passive Immunization Intranasal Immunization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Mutans streptococci

S. mutans

Streptococcus mutans


Glucan-binding protein


Antigen I/II

S. sobrinus

Streptococcus sobrinus


Surface protein antigen A


Cell wall-associated protein




Cell-associated glucosyltransferase


Culture supernatant glucosyltransferase


Gingival crevicular fluid


Immunoglobulin G


Immunoglobulin A


Immunoglobulin M


Immunoglobulin Y


Secretory immunoglobulin A


Mucosa-associated lymphoid tissue


Gut-associated lymphoid tissue

T cells

Thymus-derived lymphocytes

B cells

Bone marrow-derived lymphocytes


Major histocompatibility complex

S. mitis

Streptococcus mitis

S. salivarius

Streptococcus salivarius


Enzyme-linked immunosorbent assay


Nasal-associated lymphoid tissue


Salivary binding reception-cholera toxin


Single chain Fc


Variable domain of llama heavy chain homodimeric IgG


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  1. Alaluusua S, Renkonen OV (1983)Streptococcus mutans establishment and dental caries experience in children from 2 to 4 years old. Scand J Dent Res 91:453–457.PubMedGoogle Scholar
  2. Banas JA, Vickerman MM (2003) Glucan binding proteins of the oral streptococci. Crit Rev Oral Biol Med 14:89–99.PubMedCrossRefGoogle Scholar
  3. Banas JA, Russell RR, Ferretti JJ (1990) Sequence analysis of the gene for the glucan-binding protein ofStreptococcus mutans Ingbritt. Infect Immun 58:667–673.PubMedGoogle Scholar
  4. Beisner DR, Ch’en IL, Kolla RV, Hoffmann A, Hedrick SM (2005) Cutting edge: innate immunity conferred by B cells is regulated by caspase-8. J Immunol 175:3469–3473.PubMedGoogle Scholar
  5. Brandtzaeg P (2007) Induction of secretory immunity and memory at mucosal surfaces. Vaccine 25:5467–5484.PubMedCrossRefGoogle Scholar
  6. Brandtzaeg P, Johansen F-E (2005) Mucosal B cells: phenotypic characteristics, transcriptional regulation, and homing properties. Immunol Rev. 206:32–63.PubMedCrossRefGoogle Scholar
  7. Burne RA (1998) Oral streptococci. products of their environment. J Dent Res 77:445–452.PubMedCrossRefGoogle Scholar
  8. Camling E, Gahnberg L, Krasse B, Wallman C (1991) Crevicular IgG antibodies andStreptococcus mutans on erupting human first permanent molars. Arch Oral Biol 36:703–708.PubMedCrossRefGoogle Scholar
  9. Camling E, Gahnberg L, Emilson CG, Lindquist B (1992) Crevicular IgG antibodies and recovery ofStreptococcus mutans implanted by mouth rinsing. Scand J Dent Res 6:134–138.Google Scholar
  10. Catalanotto FA, Shklair IL, Keene HJ (1975) Prevalence and localization of Streptococcus mutans in infants and children. J Am Dent Assoc 91:606–609.PubMedGoogle Scholar
  11. Caufield PW, Cutter GR, Dasanayake AP (1993) Initial acquisition of mutans streptococci by infants: evidence for a discrete window of infectivity. J Dent Res 72:37–45.PubMedGoogle Scholar
  12. Challacombe SJ, Percival RS, Marsh PD (1995) Age-related changes in immunoglobulin isotypes in whole and parotid saliva and serum in healthy individuals. Oral Micro Immunol 10:202–207.CrossRefGoogle Scholar
  13. Childers NK, Tong G, Mitchell S, Kirk K, Russell MW, Michalek SM (1999) A controlled clinical study of the effect of nasal immunization with a Streptococcus mutans antigen alone or incorporated into liposomes on induction of immune responses. Infect Immun 67:618–623.PubMedGoogle Scholar
  14. Childers NK, Tong G, Li F, Dasanayake AP, Kirk K, Michalek SM (2002) Humans immunized withStreptococcus mutans antigens by mucosal routes. J Dent Res 81:48–52.PubMedCrossRefGoogle Scholar
  15. Cole MF, Bryan S, Evans MK, Pearce CL, Sheridan MJ, Sura PA, Wientzen RL Bowden GHW (1999) Humoral immunity to commensal oral bacteria in human infants: salivary secretory immunoglobulin A antibodies reactive withStreptococcus mitis biovar 1,Streptococcus oralis,Streptococcus mutans, andEnterococcus faecalis during the first two years of life. Infect Immun 67:1878–1886.PubMedGoogle Scholar
  16. Culshaw S, LaRosa K, Tolani H, Han X, Eastcott JW, Smith DJ, Taubman MA (2007) Immunogenic and protective potential of mutans streptococcal glucosyltransferase peptide constructs selected by major histocompatibility complex class II allele binding. Infect Immun 75:915–923.PubMedCrossRefGoogle Scholar
  17. Fitzsimmons SP, Evans MK, Pearce CL, Sheridan MJ, Wientzen R, Cole MF (1994) Immunoglobulin A subclasses in infants’ saliva and in saliva and milk from their mothers. J Pediatr 124:566–573.PubMedCrossRefGoogle Scholar
  18. Fontana M, Dunipace AJ, Stookey GK, Gregory RL (1999) Intranasal immunization against dental caries with aStreptococcus mutans-enriched fimbrial preparation. Clin Diagn Lab Immunol 6:405–409.PubMedGoogle Scholar
  19. Guo JH, Jia R, Fan MW, Bian Z, Chen Z, Peng B (2004) Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans. J Dent Res 83:266–270.PubMedCrossRefGoogle Scholar
  20. Hajishengallis G, Harokopakis E, Hollingshead SK, Russell MW, Michalek SM (1996) Construction and oral immunogenicity of aSalmonella typhimurium strain expressing a streptococcal adhesin linked to the A2/B subunits of cholera toxin. Vaccine 14:1545–1548.PubMedCrossRefGoogle Scholar
  21. Hajishengallis G, Russell MW, Michalek SM (1998) Comparison of an adherence domain and a structural region ofStreptococcus mutans antigen I/II in protective immunity against dental caries in rats after intranasal immunization. Infect Immun 66:1740–1743.PubMedGoogle Scholar
  22. Hamada S, Slade HD (1980) Biology, immunology and cariogenicity of Streptococcus mutans. Microbiol Rev 44:331–384.PubMedGoogle Scholar
  23. Hamada S, Horikoshi, T, Minami T, Kawabata S, Hiraoka J, Fujiwara T, Ooshima T (1991) Oral passive immunization against dental caries in rats by use of hen egg yolk antibodies specific for cell-associated glucosyltransferase of Streptococcus mutans. Infect Immunity 59:4161–4167.Google Scholar
  24. Hatta H, Tsuda K, Ozeki M, Kim M, Yamamoto T, Otake S, Hirasawa M, Katz J, Childers NK, Michalek SM (1997) Passive immunization against dental plaque formation in humans: effect of a mouth rinse containing egg yolk antibodies (IgY) specific to Streptococcus mutans. Caries Res 31:268–274.PubMedCrossRefGoogle Scholar
  25. Hayes JA, Adamson-Macedo EN, Perera S, Anderson J (1999) Detection of secretory immunoglobulin A (SIgA) in saliva of ventilated and non-ventilated preterm neonates. Neuro Endocrinol Lett 20:109–113.PubMedGoogle Scholar
  26. Jayashree S, Bhan MK, Kumar R, Raj P, Glass R, Bhandari N (1988) Serum and salivary antibodies as indicators of rotavirus infection in neonates. J Infect Dis 158:1117–1120.PubMedGoogle Scholar
  27. Jenkinson HF, Lamont R (2005) Oral microbial communities in sickness and in health. Trends Microbiol 13:589–595.PubMedCrossRefGoogle Scholar
  28. Jespersgaard C, Hajishengallis G, Huang Y, Russell MW, Smith DJ, Michalek SM (1999) Protective immunity againstStreptococcus mutans infection in mice after intranasal immunization with the glucan-binding region ofS. mutans glucosyltransferase. Infect Immunity 67:6543–6549.Google Scholar
  29. Kent R, Smith DJ, Joshipura K, Soparkar P, Taubman MA (1992) Humoral IgG antibodies to oral microbiota in a population at risk for root-surface caries. J Dent Res 71:1399–1407.PubMedGoogle Scholar
  30. Klein MI, Florio FM, Pereira AC, Hofling JF, Goncalves RB (2004) Longitudinal study of transmission, diversity, and stability ofStreptococcus mutans andStreptococcus sobrinus genotypes in Brazilian nursery children. J Clin Microbiol 42:4620–4626.PubMedCrossRefGoogle Scholar
  31. Koga T, Oho T, Shimazaki Y, Nakano Y (2002) Immunization against dental caries. Vaccine 20:2027–2044.PubMedCrossRefGoogle Scholar
  32. Kohler B, Andreen I, Jonsson B (1988) The earlier the colonization by mutans streptococci, the higher the caries prevalence at 4 years of age. Oral Microbiol Immunol 3:14–17.PubMedCrossRefGoogle Scholar
  33. Kruger C, Hu Y, Pan Q, Marcotte H, Hultberg A, Delwar D, van Dalen PJ, Puwels PH, Leer RJ, Kelly CG, van Dollenweerd C, Ma JK, Hammarstrom L (2002)In situ delivery of passive immunity by lactobacilli producing single-chain antibodies. Nature Biotech 20:702–706.CrossRefGoogle Scholar
  34. Kruger C, Pearson SK, Kodama Y, Vacca Smith A, Bowen WH, Hammarstrom L (2004) The effects of egg-derived antibodies to glucosyltransferases on dental caries in rats. Caries Res 38:9–14.PubMedGoogle Scholar
  35. Kruger C, Hultberg A, van Dollenweerd C, Marcotte H, Hammarstrom L (2005) Passive immunization by lactobacilli expressing single-chain antibodies against Streptococcus mutans. Mol Biotechnol 31:221–231.PubMedCrossRefGoogle Scholar
  36. Kruger C, Hultberg A, Marcotte H, Hermans P, Bezemer S, Frenken LGJ, Hammarstrom L (2006) Therapeutic effect of llama derived VHH fragments againstStreptococcus mutans on the development of dental caries. Appl Microbiol Biotechnol 72: 732–737.PubMedCrossRefGoogle Scholar
  37. Jia R, Gao JH, Fan MW, Bian Z, Chen Z, Peng B, Fan B (2004) Mucosal immunization against dental caries with plasmid DNA encodingpac gene ofStreptococcus mutans in rats. Vaccine 22:2511–2516.PubMedCrossRefGoogle Scholar
  38. Johansen F-E, Baekkevold ES, Carlsen HS, Farstad IN, Soler D, Brandtzaeg P (2005) Regional induction of adhesion molecules and chemokine receptors explains disparate homing of human B cells to systemic and mucosal effector sites: dispersion from tonsils. Blood 106:593–600.PubMedCrossRefGoogle Scholar
  39. Lehner T, Russell MW, Challacombe SJ, Scully CM, Hawkes JE (1978) Passive immunization with serum and immunoglobulins against dental caries in rhesus monkeys. Lancet 1:693–695.PubMedCrossRefGoogle Scholar
  40. Lehner T, Caldwell J, Smith R (1985) Local passive immunization by monoclonal antibodies against streptococcal antigen I/II in the prevention of dental caries. Infect Immunity 50:796–799.Google Scholar
  41. Li Y, Caufield PW (1995) The fidelity of initial acquisition of mutans streptococci by infants from their mothers. J Dent Res 74:681–685.PubMedCrossRefGoogle Scholar
  42. Loesche WJ (1986) Role ofStreptococcus mutans in human dental decay. Microbiol Rev 50:353–380.PubMedGoogle Scholar
  43. Loimaranta V, Laine M, Soderling E, Vasara E, Rokka S, Marnila P, Korhonen H, Tossavainen O, Tenovuo J (1999) Effects of bovine immune and non/immune whey preparations on the composition and pH responses of human dental plaque. Eur J Oral Sci 107:244–250.PubMedCrossRefGoogle Scholar
  44. Luo Z, Smith DJ, Taubman MA, King WF (1988) Cross sectional analysis of serum antibody to oral streptococcal antigens in children. J Dent Res 67:554–560.PubMedGoogle Scholar
  45. Ma JK, Lehner T (1990) Prevention of colonization of Streptococcus mutans by topical application of monoclonal antibodies in human subjects. Archs Oral Biol 35 Suppl:115S–122S.CrossRefGoogle Scholar
  46. Ma JK, Hunjan M, Smith R, Kelly C, Lehner T (1990) An investigation into the mechanism of protection by local passive immunization with monoclonal antibodies against Streptococcus mutans. Infect Immunity 58:3407–3414.Google Scholar
  47. Ma JK, Hikmat BY, Wycoff K, Vine ND, Chargelegue D, Yu L, Hein MB, Lehner T (1998) Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nature Med 4:601–606.PubMedCrossRefGoogle Scholar
  48. Macpherson AJ, Gatto D, Sainsbury E, Harriman GR, Hengartner H, Zinkernagel RM (2000) A primitive T cell-independent mechanism of intestinal mucosal IgA responses to commensal bacteria. Science 288:2222–2226.PubMedCrossRefGoogle Scholar
  49. Macpherson AJ, Geuking MB, McCoy KD (2005) Immune responses that adapt the intestinal mucosa to commensal intestinal bacteria. Immunology 115:153–162.PubMedCrossRefGoogle Scholar
  50. Martin M, Metzger DJ, Michalek SM, Connell TD, Russell MW (2000) Comparative analysis of the mucosal adjuvanticity of the type II heat-labile enterotoxins LT-IIa and LT-IIb. Infect Immun 68:281–287.PubMedCrossRefGoogle Scholar
  51. Mattos-Graner RO, Rontani RM, Gaviao MB, Bocatto HA (1996) Caries prevalence in 6–36-month-old Brazilian children. Community Dent Health 13:96–98.Google Scholar
  52. Mattos-Graner RO, Smith DJ, King WF, Mayer MPA (2000) Water-insoluble glucan synthesis by mutans streptococcal strains correlates with caries incidence in 12- to 30-month-old children. J Dent Res 79:1371–1377.PubMedCrossRefGoogle Scholar
  53. Mattos-Graner RO, Correa MS, Latorre MR, Peres RC, Mayer MP (2001a) Mutans streptococci oral colonization in 12–30-month-old Brazilian children over a one-year follow-up period. J Public Health Dent 61:161–167.PubMedCrossRefGoogle Scholar
  54. Mattos-Graner RO, Li Y, Caufield PW, Duncan M, Smith DJ (2001b) Genotypic diversity of mutans streptococci in Brazilian nursery children suggests horizontal transmission. J Clin Microbiol 39:2313–2316.PubMedCrossRefGoogle Scholar
  55. Mellander L, Carlsson B, Hanson LA (1984) Appearance of secretory IgM and IgA antibodies toE. coli in early infancy and childhood. J Pediatr 104:564–568.PubMedCrossRefGoogle Scholar
  56. Michalek SM, Childers NK (1990) Development and outlook for a caries vaccine. Crit Rev Biol Med 1:37–54.Google Scholar
  57. Michalek SM, McGhee JR (1977) Effective immunity to dental caries: passive transfer to rats of antibody toStreptococcus mutans elicit protection. Infect Immunity 17:644–650.Google Scholar
  58. Newburg DS, Walker WA (2007) Protection of the neonate by the innate immune system of developing gut and of human milk. Pediatr Res 61:2–8.PubMedCrossRefGoogle Scholar
  59. Nogueira RD, Alves AC, Napimoga MH, Smith DJ, Mattos-Graner RO (2005) Characterization of salivary IgA responses in children heavily exposed to the oral bacteriaStreptococcus mutans: influence of specific antigen recognition in infection. Infect Immun 73:5675–5684.PubMedCrossRefGoogle Scholar
  60. Otake S, Nishahara Y, Makinura M, Hatta H, Kim M, Yamamoto T, Hirasawa T (1991) Protection of rats against dental caries by passive immunization with hen-egg yolk antibody (IgY). J Dent Res 70:162–166.PubMedGoogle Scholar
  61. Percival RS, Marsh PD, Challacombe SJ (1997) Age-related changes in salivary antibodies to commensal oral and gut biota. Oral Micro Immunol 12:57–63.CrossRefGoogle Scholar
  62. Quivey RG, Kuhnert WL, Hahn K (2001) Genetics of acid adaptation in oral streptococci. Crit Rev Oral Biol Med 12:301–314.PubMedCrossRefGoogle Scholar
  63. Quan CP, Berneman A, Pires R, Avrameas S, Bouvet JP (1997) Natural polyreactive secretory immunoglobulin A autoantibodies as a possible barrier to infection in humans. Infect Immun 65:3997–4004.PubMedGoogle Scholar
  64. Redman TK, Harmon CC, Michalek SM (1996) Oral immunization with recombinantSalmonella typhimurium expressing surface protein antigen A (SpaA) of Streptococcus sobrinus: effects of the Salmonella virulence plasmid on the induction of protective and sustained humoral responses in rats. Vaccine 14:868–878.PubMedCrossRefGoogle Scholar
  65. Russell MW, Lehner T (1978) Characterization of antigens extracted from cells and culture supernatant fluids ofStreptococcus mutans serotype c. Archs Oral Biol 23:7–15.CrossRefGoogle Scholar
  66. Russell MW, Wu HY (1991) Distribution, persistence, and recall of serum and salivary antibody responses to peroral immunization with protein antigen I/II ofStreptococcus mutans coupled to the cholera toxin B subunit. Infect Immun 59:4061–4070.PubMedGoogle Scholar
  67. Russell MW, Hajishengallis G, Childers NK, Michalek SM (1999) Secretory immunity in defense against cariogenic mutans streptococci. Caries Res. 33:4–15.PubMedCrossRefGoogle Scholar
  68. Saarela M, Alaluusua S, Takei T, Asikainen S (1993) Genetic diversity within isolates of mutans streptococci recognized by an rRNA gene probe. J Clin Microbiol 31:584–587.PubMedGoogle Scholar
  69. Sato Y, Yamamoto Y, Harutoshi K (1997) Cloning and sequence analysis of the GbpC gene encoding a novel glucan-binding protein of Streptococcus mutans. Infect Immun 65:668–675.PubMedGoogle Scholar
  70. Schour I, Massler M (1962) The Teeth. In: Farris E, Griffith J (eds) Hafner, New York, p 106.Google Scholar
  71. Seifert TB, Bleiweis AS, Brady LJ (2004) Contribution of the alanine-rich region ofStreptococcus mutans P1 to antigenicity, surface expression, and interaction with the proline-rich repeat domain. Infect Immun 72:4699–4706.PubMedCrossRefGoogle Scholar
  72. Senadheera MD, Guggenheim B, Spatafora GA, Huang YC, Choi J, Hung DC, Treglown JS, Goodman SD, Ellen RP, Cvitkovitch DG (2005) A VicRK signal transduction system inStreptococcus mutans affectsgtfBCD,gbpB, andftf expression, biofilm formation, and genetic competence development. J Bacteriol 187:4064–4076.PubMedCrossRefGoogle Scholar
  73. Senadheera MD, Lee AW, Huang DC, Spatafora GA, Goodman SD, Cvitkovitch DG (2007) TheStreptococcus mutans vicX gene product modulates gtfB/C expression, biofilm formation, genetic competence, and oxidative stress tolerance. J Bacteriol 189:1451–1458.PubMedCrossRefGoogle Scholar
  74. Shah DS, Russell RR (2004) A novel glucan-binding protein with lipase activity from the oral pathogen Streptococcus mutans. Microbiology 150:1947–1956.PubMedCrossRefGoogle Scholar
  75. Shimazaki Y, Mitoma M, Oho T, Nakano Y, Yamashita Y, Okano K, Fujiyama M, Fujihara N, Nada Y, Koga T (2001) Passive immunization with milk produced from an immunized cow prevents oral recolonization by Streptococcus mutans. Clin Diagn Lab Immunol 8:1136–1139.PubMedGoogle Scholar
  76. Smith DJ (2002) Dental caries vaccines: Prospects and concerns. Crit Rev Oral Biol Med 13:335–349.PubMedCrossRefGoogle Scholar
  77. Smith DJ, Taubman MA (1987) Oral immunization of humans withStreptococcus sobrinus glucosyltransferase. Infect Immun 55:2562–2569.PubMedGoogle Scholar
  78. Smith DJ, Taubman MA (1987) Ontogeny and senescence of salivary immunity. J Dent Res 66:451–456.PubMedGoogle Scholar
  79. Smith DJ, Taubman MA (1990) Effect of local deposition of antigen on salivary immune responses and reaccumulation of mutans streptococci. J Clin Immunol 10:273–281.PubMedCrossRefGoogle Scholar
  80. Smith DJ, Taubman MA (1992) Ontogeny of immunity to oral microbiota. Crit Rev Oral Biol Med 3:109–133.PubMedGoogle Scholar
  81. Smith DJ, Taubman MA (1993) Emergence of immune mechanisms in saliva. Crit Rev Oral Med 4:335–341.Google Scholar
  82. Smith DJ, Taubman MA (1996) Experimental immunization of rats with aStreptococcus mutans 59-kilodalton glucan-binding protein protects against dental caries. Infect Immun 64:3069–3073.PubMedGoogle Scholar
  83. Smith DJ, King WF, Taubman MA (1989) Isotype, subclass and molecular size of immunoglobulins in salivas from young infants. Clin Exper Immunol 76:97–102.Google Scholar
  84. Smith DJ, Akita H, King WF, Taubman MA (1994) Purification and antigenicity of a novel glucan binding protein of S. mutans. Infect Immun 62:2545–2552.PubMedGoogle Scholar
  85. Smith DJ, Heschel R, Melvin J, King WF, Pereira MBB, Taubman MA (1997)Streptococcus mutans glucan binding proteins as dental caries vaccines. In: Husband AJ, Beagley KW, Clancey RL, et al (eds) Mucosal Solutions: Advances in Mucosal Immunology. University of Sydney, Sydney, pp 367–377.Google Scholar
  86. Smith DJ, King WF, Akita H, Taubman MA (1998) Association of salivary IgA antibody and initial mutans streptococcal infection. Oral Micro Immunol 13:278–285.CrossRefGoogle Scholar
  87. Smith DJ, King WF, Barnes LA, Trantolo D, Wise DL, Taubman MA (2001a) Facilitated intranasal induction of mucosal and systemic immunity to mutans streptococcal glucosyltransferase peptide vaccines. Infect Immun 69:4767–4773.PubMedCrossRefGoogle Scholar
  88. Smith DJ, King WF, Godiska R (2001b) Passive transfer of immunoglobulin Y antibody toStreptococcus mutans glucan binding protein B can confer protection against experimental dental caries. Infect Immunity 69:3135–3142.CrossRefGoogle Scholar
  89. Smith DJ, King WF, Barnes LA, Peacock Z, Taubman MA (2003a) Immunogenicity and protective immunity induced by synthetic peptides associated with putative immunodominant regions ofStreptococcus mutans glucan-binding protein B. Infect Immun 71:1179–1184.PubMedCrossRefGoogle Scholar
  90. Smith DJ, Lam A, Barnes LA, King WF, Peacock Z, Wise DL, Trantolo DJ, Taubman MA (2003b) Remote glucosyltransferase-microparticle vaccine delivery induces protective immunity in the oral cavity. Oral Micro Immunol 18:240–248.CrossRefGoogle Scholar
  91. Smith DJ, King WF, Rivero J, Taubman MA (2005) Immunological and protective effect of diepitopic subunit dental caries vaccines. Infect Immun 73:2797–2804.PubMedCrossRefGoogle Scholar
  92. Takahashi I, Okahashi N, Matsushita K, Tokuda M, Kanamoto T, Munekata E et al (1991) Immunogenicity and protective effect against oral colonization byStreptococcus mutans of synthetic peptides of a streptococcal surface protein antigen. J Immunol 146:332–336.PubMedGoogle Scholar
  93. Tanner AC, Milgrom PM, Kent R Jr, Mokeem SA, Page RC, Liao SI et al (2002) Similarity of the oral microbiota of pre-school children with that of their caregivers in a population-based study. Oral Microbiol Immunol 17:379–387.PubMedCrossRefGoogle Scholar
  94. Tanzer JM (1995) Dental caries is a transmissible infectious disease: the Keyes and Fitzgerald revolution. J Dent Res 74:1536–1542.PubMedCrossRefGoogle Scholar
  95. Tanzer JM, Livingston J, Thompson AM (2001) The microbiology of primary dental caries in humans. J Dent Educ 65:1028–1037.PubMedGoogle Scholar
  96. Taubman MA, Nash D (2006) The scientific and public health imperative for a dental caries vaccine. Nat Rev Immunol 6:555–563.PubMedCrossRefGoogle Scholar
  97. Taubman MA, Holmberg CJ, Smith DJ (2001) Diepitopic construct of functionally and epitopically complementary peptides enhances immunogenicity, reactivity with glucosyltransferase, and protection from dental caries. Infect Immun 69:4210–4216.PubMedCrossRefGoogle Scholar
  98. Taubman MA, Orr N, Smith DJ, Eastcott J, Hayden T (2002) A rodent model for analysis of immunization with GTF peptides expressed in attenuated Salmonella enterica. Mucosal Immunol Update. 10: 2553.Google Scholar
  99. van Ginkel FW, Jackson RJ, Yuki Y, McGhee JM (2000) Cutting edge: the mucosal adjuvant cholera toxin redirects vaccine proteins into olfactory tissues. J Immunol 165:4778–4782.PubMedGoogle Scholar
  100. Weintraub JA, Hilton JF, White JM, Hoover CI, Wycoff KL, Yu L, Larrick JW, Featherstone JDB (2005) Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res 39:241–250.PubMedCrossRefGoogle Scholar
  101. Whiley RA, Beighton D (1998) Current classification of the oral streptococci. Oral Microbiol Immunol 13:195–216.PubMedCrossRefGoogle Scholar
  102. Yu H, Nakano Y, Yamashita Y, Oho T, Koga T (1997) Effects of antibodies against cell surface protein antigen PAc-glucosyltransferase fusion proteins on glucan synthesis and cell adhesion of Streptococcus mutans. Infect Immun 65:2292–2298.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • D. J. Smith
    • 1
  • R. O. Mattos-Graner
  1. 1.Department of ImmunologyThe Forsyth InstituteBostonUSA

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