Caries vaccine

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A caries vaccine is a vaccine to prevent and protect against tooth decay.[1] Streptococcus mutans (S. mutans) has been identified as the major etiological agent of human dental caries. The development of a vaccine for tooth decay has been under investigation for more than 30 years. In 1972, a caries vaccine was said to be in animal testing in England, and that it would have begun human testing soon.[2] Intrinsic difficulties in developing it, coupled with lack of strong economic interests, are the reasons why no such vaccine is commercially available as of 2018. Several types of vaccines are being developed at research centres, with some kind of caries vaccines being considered to diminish or prevent dental caries' impact on the young group.[3]

Attempts using antibodies[edit]

Early attempts followed a traditional approach to vaccination where normal S. mutans was introduced to promote a reaction from the immune system, stimulating antibody production.[4]

Planet Biotechnology developed a monoclonal antibody against S. mutans, branded CaroRx, produced with transgenic tobacco plants. It is a therapeutic vaccine, applied once every several months. Phase II clinical trials were discontinued in 2016.

The International Association for Dental Research and American Association for Dental Research announced a study performed by the Chinese Academy of Sciences which looked at using an inhaled vaccine that uses a protein filament as a delivery vehicle. Trials performed in rats showed an increase in antibody response along with a decrease in the amount of Streptococcus mutans adhering to teeth, leading to significantly fewer cavities observed among the test population.[5]

Attempts using replacement therapy[edit]

On a different line of research, Jeffrey Hillman from the University of Florida[6] developed a genetically modified strain of Streptococcus mutans called BCS3-L1, that is incapable of producing lactic acid – the acid that dissolves tooth enamel – and aggressively replaces native flora. In laboratory tests, rats who were given BCS3-L1 were conferred with a lifetime of protection against S. mutans.[7] BCS3-L1 colonizes the mouth and produces a small amount of a lantibiotic, called MU1140,[7] which allows it to out-compete S. mutans.[8] Hillman suggested that treatment with BCS3-L1 in humans could also provide a lifetime of protection, or, at worst, require occasional re-applications. He stated that the treatment would be available in dentists' offices and "will probably cost less than $100."[9] The product was being developed by Oragenics, but was shelved in 2014, citing regulatory concerns and patent issues.[10] In 2016, Oragenics received a 17-year patent for the product.[11]

On rare occasions the native S. mutans strain escapes into the blood, potentially causing dangerous heart infections. It is unclear how likely BCS3-L1 is to do the same.[12]

Another approach is being pursued by BASF, focused on replacing native lactobacillus flora with a variety dubbed L. anti-caries, which prevents S. mutans from binding to enamel.[13] However, it is not a long-term vaccination in that no attempt is being made to have a self-sustaining population of L. anti-caries. The intent is that the L. anti-caries population would be frequently replenished through use of a chewing gum containing the organism.

The University of Leeds has also begun researching a recently discovered peptide known as P11-4. When applied to a cavity and coming in contact with saliva, this peptide assembles itself in a fibrous matrix or scaffold, attracting calcium and thereby allowing the tooth to regenerate.[14][15] The Swiss-based company Credentis has licensed the peptide and launched a product called Curodont Repair in 2013.[16] Recent studies show a positive clinical effect.[17]

DNA vaccines[edit]

DNA vaccine approaches for dental cavities have had a history of success in animal models. Dental cavity vaccines directed to key components of S. mutans colonization and enhanced by safe and effective adjuvants and optimal delivery vehicles, are likely to be forthcoming. S. mutans believe that rational target for developing an anti-caries vaccine is protein antigen, which has an adherent functional and important immunogenic regions.[18]

Bacteriophage treatment[edit]

The use of Enterococcus faecalis bacteriophages as a form of treatment for caries has been considered, as they are capable of maintaining persistent stability in human saliva.[19]

References[edit]

  1. ^ "Panel on Caries Vaccine". National Institute of Dental and Craniofacial Research of the National Institute of Health. January 28, 2003. Archived from the original on 2011-08-24. Retrieved 14 April 2008.
  2. ^ Bowen, W.H. (December 1972). "Dental caries". Archives of Disease in Childhood. 47 (256): 849–53. doi:10.1136/adc.47.256.849. PMC 1648396. PMID 4567073.
  3. ^ Richie, Chhabra; Karan, Rajpal (Jan 2016). "Caries vaccine: A boom for public health". Annals of Tropical Medicine & Public Health. 9 (1): 1–3. doi:10.4103/1755-6783.168715.
  4. ^ Martin A. Taubman; Daniel J. Smith (June 1974). "Effects of Local Immunization with Streptococcus mutans on Induction of Salivary Immunoglobulin A Antibody and Experimental Dental Caries in Rats". Infection and Immunity. 9 (6): 1079–1091. PMC 414936. PMID 4545425.
  5. ^ Yang, Jingyi; Sun, Ying; Bao, Rong; Zhou, Dihan; Yang, Yi; Cao, Yuan; Yu, Jie; Zhao, Bali; Li, Yaoming; Yan, Huimin; Zhong, Maohua (2017). "Second-generation Flagellin-rPAc Fusion Protein, KFD2-rPAc, Shows High Protective Efficacy against Dental Caries with Low Potential Side Effects". Scientific Reports. 7 (1): 11191. doi:10.1038/s41598-017-10247-8. PMC 5593867. PMID 28894188.
  6. ^ "This Germ Could Save Your Life". Popular Science. Retrieved 2016-09-20.
  7. ^ a b "Replacement Therapy". ONI Biopharma. Retrieved 6 January 2009.
  8. ^ Hillman, Jeffrey D. (August 2002). "Genetically modified Streptococcus mutans for the prevention of dental caries". Antonie van Leeuwenhoek. 82 (1–4): 361–366. doi:10.1023/A:1020695902160. PMID 12369203.
  9. ^ "Genetically modified bacteria may prevent caries". HealthMantra. January 2002. Retrieved 2006-12-18.
  10. ^ "Wall Street Journal Interview with Oragenics' CEO, Dr. John Bonfiglio - Transcript" (PDF). April 2014. Archived from the original (PDF) on 2014-05-02. Retrieved 2014-05-01.
  11. ^ "Oragenics Receives New Patent for Improved Replacement Therapy for Dental Caries". Retrieved 8 January 2017.
  12. ^ "Wash that mouth out with bacteria!". Science News. 18 March 2000.
  13. ^ "Chewing gum with added bite". British Dental Journal. 201 (5): 255. 2006. doi:10.1038/sj.bdj.4814014.
  14. ^ "Breakthrough could make dental drills obsolete". Healthier Talk. 9 April 2011.
  15. ^ S Kyle; A Aggeli; M J McPherson; E Ingham (2008). "THE SELF-ASSEMBLING PEPTIDE, P11-4 AS A SCAFFOLD FOR USE IN REGENERATIVE MEDICINE" (PDF). European Cells & Materials. 16 (3): 70. ISSN 1473-2262.
  16. ^ "New Treatment Fixes Tooth Decay Without Drilling". Science Business. 24 August 2011.
  17. ^ Schlee, M.; Rathe, F.; Huck, T.; Schad, T.; Koch, J.H.; Tjaden, A.; Bommer, C. (19 July 2014). "Klinischer Effekt biomimetischer Mineralisation bei Approximalkaries". Stomatologie. 111 (4–5): 175–181. doi:10.1007/s00715-014-0335-4.
  18. ^ Guo, JH; Jia, R; Fan, MW; Bian, Z; Chen, Z; Peng, B (Mar 2004). "Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans". Journal of Dental Research. 83 (3): 266–270. doi:10.1177/154405910408300316. PMID 14981132.
  19. ^ G. Bachrach; M. Leizerovici-Zigmond; A. Zlotkin; R. Naor; D. Steinberg (December 2002). "Bacteriophage isolation from human saliva". Letters in Applied Microbiology. 36 (1): 50–53. doi:10.1046/j.1472-765X.2003.01262.x. PMID 12485342.