AiM  Vol.4 No.13 , October 2014
Vaccine against Dental Caries: An Update

Dental caries, the disease that causes tooth decay, is infectious, and the mutans streptococci bacteria have long been identified as the primary disease-causing agents. Caries vaccines showed promising results in experimental studies; however, it remains far the effective use in humans due to political-economic and ethical issues. Progress towards practical vaccine development requires evaluation of candidate vaccines in clinical trials. Promising strategies of passive immunization also require further clinical evaluation. The purpose of this chapter is to review the literature on the main research projects aimed at developing caries vaccines.

Cite this paper: Silva, D. , Silva, A. , Filho, R. , Verli, F. and Marinho, S. (2014) Vaccine against Dental Caries: An Update. Advances in Microbiology, 4, 925-933. doi: 10.4236/aim.2014.413103.

[1]   Keyes, P.H. (1960) The Infectious and Transmissible Nature of Experimental Dental Caries. Archives of Oral Biology, 1, 304-320.

[2]   Loesche, W.J. (1986) Role of Streptococcus mutans in Human Dental Decay. Microbiology Reviews, 50, 353-380.

[3]   Marsh, P.D and Bradshaw, D.J. (1995) Dental Plaque as a Biofilm. Journal of Industrial Microbiology, 15, 169-175.

[4]   Bowen, W.H and Koo, H. (2011) Biology of Streptococcus mutans Derived Glucosyltransferases: Role in Extracellular Matrix Formation of Cariogenic Biofilms. Caries Research, 45, 69-86.

[5]   Featherstone, J.D.B. (2000) The Science and Practice of Caries Prevention. The Journal of the American Dental Association, 131, 887-899.

[6]   Balakrishman, M., Simmonds, R.S and Tagg, J.R. (2000) Dental Caries Is a Preventable Infectious Disease. Australian Dental Journal, Sydney, 45, 235-245.

[7]   Michalek, S.M and Childers, N.K. (1990) Developmental and Outlook for Caries Vaccine. Critical Reviews in Oral Biology and Medicine, Alexandria, 1, 37-54.

[8]   Russel, M.W., Childers, N.K., Michalek, S.M., Smith, D.J. and Taubman, M.A. (2004) A Caries Vaccine? The State of the Science of Immunization against Dental Caries. Caries Research, 38, 230-235.

[9]   Xu, Q.A., Yu, F., Fan, M., Bian, Z., Guo, J., Jia, R., Chen, Z., Peng, B and Fan, B. (2005) Immunogenicity and Protective efficacy of Targeted Fusion DNA Construct against Dental Caries. Caries Research, 39, 422-421.

[10]   Zhang, F., Li, Y.H., Fan, M.W., Jia, R., Xu, K.A., Guo, J.H., Yu, F. and Tian, K.W. (2007) Enhanced Efficacy of CTLA-4 Fusion Anticaries DNA Vaccines in Gnotobiotic Hamsters. Acta Pharmacologica Sinica, 28, 1236-1242.

[11]   Yang, Y.P., Li, Y.H., Bi, L. and Fan, M.W. (2009) Good Manufacturing Practices Production and Analysis of DNA Vaccine against Dental Caries. Acta Pharmacologica Sinica, 30, 1513-1521.

[12]   Featherstone, J.D.B. (1999) Prevention and Reversal of Dental Caries: Role of Low Level Fluoride. Community Dentistry and Oral Epidemiology, 27, 31-40.

[13]   Bagramian, R.A., Garcia-Godoy, F. and Volpe, A. (2009) The Global Increase in Dental Caries. A Pending Public Health Crisis. American Journal of Dentistry, 22, 3-8.

[14]   Levine, M., Owen, W.L. and Avery, K.T. (2005) Antibody Response to Actinomyces Antigen and Dental Caries Experience: Implications for Caries Susceptibility. Clinical and Diagnostic Laboratory Immunology, 12, 764-769.

[15]   Robinette, R.A., Oli, M.W., Mcarthur, W.P. and Brady, L.J. (2011) A Therapeutic Anti-Streptococcus mutans Monoclonal Antibody Used in Human Passive Protection Trials Influences the Adaptive Immune Response. Vaccine, 29, 6292-6300.

[16]   Russel, R.R.B. (2011) Pode o controle da cárie envolver imunizacao e terapia genética? In: Fejerskov, O. and Kidd, E., Eds., Cárie Dentária: A doenca e seu tratamento Clínico, 2a Edicao, Editora Santos, Sao Paulo, 640.

[17]   Morrier, J.J. and Barsoti, O. (1990) Secretory IgA and the Oral Cavity: General Review. Actualites Odonto-Stomatologiques, 44, 349-363.

[18]   Hofling, J.F. and Goncalves, R.B. (2006) Imunologia para odontologia. Editora Artmed, Porto Alegre, 310.

[19]   Shivakumar, K.M., Vidya, S.K. and Chandu, G.N. (2009) Dental Caries Vaccine. Indian Journal of Dental Research, 20, 99-106.

[20]   Ma, J.K.C., Hunjan, M., Smith, R., Kelly, C. and Lehner, T. (1990) An Investigation into the Mechanism of Protection by Local Passive Immunization with Monoclonal Antibodies against Streptococcus mutans. Infection and Immunity, 58, 3407-3414.

[21]   Oli, M.W., Rhodin, N., Mcarthur, W.P. and Brady, L.J. (2004) Redirecting the Humoral Immune Response against Streptococcus mutans Antigen p1 with Monoclonal Antibodies. Infection and Immunity, 72, 6951-6960.

[22]   Nogueira, R.D., Alves, A.C., Napimoga, M.H., Smith, D.J. and Mattos-Graner, R.O. (2005) Characterization of Salivary Immunoglobulin a Responses in Children Heavily Exposed to the Oral Bacterium Streptococcus mutans: Influence of Specific Antigen Recognition in Infection. Infection and Immunity, 73, 5675-5684.

[23]   Chen, F. and Wang, D. (2010) Novel Technologies for the Prevention and Treatment of Dental. Expert Opinion on Therapeutic Patents, 20, 681-694.

[24]   Taubman, M.A., Holmberg, C.J. and Smith, D.J. (1995) Immunization of Rats with Synthetic Peptide Constructs from the Glucan Biding or Catalytic Region of Mutans. Infection and Immunity, 63, 3088-3093.

[25]   Russel, M.W., Hajishengallis, G., Childers, N.K. and Michalek, S.M. (1999) Secretory Immunity in Defense against Cariogenic Mutans Streptococci. Caries Research, 33, 4-15.

[26]   Hajishengallis, G. and Michalek, S.M. (1998) Current Status of a Mucosal Vaccine against Dental Caries. Oral Microbiology and Immunology, 13, 326-345.

[27]   Lehner, T., Russell, M.W., Caldwell, J. and Smith, R. (1981) Immunization with Purified protein Antigens from Streptococcus mutans against Dental Caries in Rhesus Monkeys. Infection and Immunity, 34, 407-415.

[28]   Xu, Q.A., Yu, F., Fan, M.W., Bian, Z., Chen, Z., Fan, B., Jia, R. and Guo, J.H. (2006) Immunogenicity and Persistence of a Targeted Anti-Caries DNA Vaccine. Journal of Dental Research, 85, 915-918.

[29]   Xu, Q.A., Yu, F., Fan, M.W., Bian, Z., Chen, Z., Peng, B., Jia, R. and Guo, J.H. (2007) Protective Efficacy of a Targeted Anti-Caries DNA Plasmid against Cariogenic Bacteria Infections. Vaccine, 25, 1191-1195.

[30]   Mitoma, M., Oho, T., Michibata, N., Okano, K., Nakano, Y., Fukuyama, M. and Koga, T. (2002) Passive Immunization with Bovine Milk Containing Antibodies to a Cell Surface Protein Antigen-Glucosyltransferase Fusion Protein Protects Rats against Dental Caries. Infection and Immunity, 70, 2721-2724.

[31]   Ooshima, T., Sobue, S., Hamada, S. and Kotani, S. (1981) Susceptibility of Rats, Hamsters, and Mice to Carious Infection by Streptococcus mutans Serotype c and d Organisms. Journal of Dental Research, 60, 855-859.

[32]   Soet, J.J., Van loveren, C., Lammens, A.J., Pavinic, M.J., Homburg, C.H., Ten Cate, J.M. and Graaff, J. (1991) Differences in Cariogenicity between Fresh Isolates of Streptococcus sobrinus and Streptococcus mutans. Caries Research, 25, 116-122.

[33]   Russel, R.R.B. and Colman, G. (1981) Immunization of Monkey (Macaca fascicularis) with Purified streptococcus mutans Glucosyltransferase. Archives of Oral Biology, 26, 23-28.

[34]   Ayakawa, G.Y., Bleiweis, A.S., Crowley, P.J. and Cunningham, M.W. (1988) Heart Cross-Reactive Antigens of Mutans Streptococci Share Epitopes with Group A Streptococci and Myosin. Journal of Immunology, 140, 253-257.

[35]   Canattieri, A.C.V., Kretchetoff, F.Y., Ito, C.I.K., Moreira, D., Fujarra, R.J.C. and Unterkircher, C.S. (2006) Production of Monoclonal Antibodies against Streptococcus mutans Antigens. Brazilian Oral Research, 20, 297-302.

[36]   Zhang, P., Jespersgaard, C., Lamberty-Mallorry, L., Katz, J., Huang, Y., Hajishengallis, G. and Michaleki, S.M. (2002) Enhanced Immunogenicity of a Genetic Chimeric Protein Consisting of Two Virulence Antigens of Streptococcus mutans and Protection against Infection. Infection and Immunity, 70, 6779-6787.

[37]   Ajdic, D., Mcshan, W.M., Mclaughlin, R.E., Savic, G., Chang, J., Carson, M.B., Primeaux, C., Tian, R.Y., Kenton, S., Jia, H.G., Lin, S.P., Qian, Y.D., Li, S.L., Zhu, H., Najar, F., Lai, H.S., White, J., Roe, B.A. and Ferretti, J.J. (2002) Genome Sequence of Streptococcus mutans UA159, a Cariogenic Dental Pathogen. Proceedings of the National Academy of Sciences of the United States of America, 99, 14434-14439.

[38]   Smith, D.J., King, W.F., Rivero, J. and Taubman, M.A. (2005) Immunological and Protection Effects Diepitopic Subunit Dental Caries Vaccines. Infection and Immunity, 73, 2797-2804.

[39]   Waterhouse, J.C. and Roy, R.B. (2006) Dispensable Genes and Foreign DNA in Streptococcus mutans. Microbiology, 152, 1777-1788.

[40]   Hoshino, T., Kondo, Y., Saito, K., Terao, Y., Okahashi, N., Kawabata, S. and Fujiwara, T. (2011) Novel Epitopic Region of Glucosyltransferase B from Streptococcus mutans. Clinical and Vaccine Immunology, 18, 1552-1561.

[41]   Liu, C., Fan, M., Xu, Q.A. and Li, Y.H. (2008) Biodistribution and Expression of Targeted Fusion Anti-Caries DNA Vaccine pGJA-P/VAX in Mice. Journal of Gene Medicine, 10, 298-305.

[42]   Jia, R., Guo, J.H., Fan, M.W., Bian, Z., Fan, B., Yu, F. and Xu, Q.A. (2006) Immunogenicity of CTLA4 Fusion Anti-Caries DNA Vaccine in Rabbits and Monkeys. Vaccine, 24, 5192-5200.

[43]   Fan, M.W., Bian, Z., Peng, Z.X., Zhong, Y., Chen, Z., Peng, B. and Jia, R. (2002) A DNA Vaccine Encoding a Cell-Surface Protein Antigen of Streptococcus mutans Protects Gnotobiotic Rats from Caries. Journal of Dental Research, 81, 784-787.

[44]   Niu, Y., Sun, J., Fan, M., Xu, Q.A., Guo, J., Jia, R. and Li, Y. (2009) Construction of a New Fusion Anti-Caries DNA Vaccine. Journal of Dental Research, 88, 455-460.

[45]   Chen, L., Zhu, J., Li, Y., Lu, J., Gao, L., Xu, H., Fan, M. and Yang, X.L. (2013) Enhanced Nasal Mucosal Delivery and Immunogenicity of Anti-Caries DNA Vaccine through Incorporation of Anionic Liposomes in Chitosan/DNA Complexes. PLoS ONE, 8, e71953.

[46]   Su, L.K., Yu, F., Li, Z., Zeng, C., Xu, Q.A. and Fan, M.W. (2014) Intranasal Co-Delivery of IL-6 Gene Enhances the Immunogenicity of Anti-Caries DNA Vaccine. Acta Pharmacologica Sinica, 35, 592-598.

[47]   Kelly, C.G., Younson, J.S., Hikmat, B.Y., Todryk, S.M., Czisch, M., Haris, P.I., et al. (1999) A Synthetic Peptide Adhesion Epitope as a Novel Antimicrobial Agent. Nature Biotechnology, 17, 42-47.

[48]   Younson, J. and Kelly, C.G. (2004) The Rational Design of an Anti-Caries Peptide against Streptococcus mutans. Molecular Diversity, 8, 121-126.

[49]   Jakubovics, N.S., Stromberg, N., Van Dolleweerd, C.J., Kelly, C.G. and Jenkinson, H.F. (2005) Differential Binding Specificities of Oral Streptococcal Antigen I/II Family Adhesins for Human or Bacterial Ligands. Molecular Microbiology, 55, 1591-1605.

[50]   Smith, D.J. (2010) Dental Caries Vaccines: Prospects and Concerns. Expert Review of Vaccines, 9, 1-3.