Caries vaccine

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.

Several types of vaccines are being developed at research centres.

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 2014.

Attempts using Antibodies

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.[3]

The corporation Planet Biotechnology has developed a synthetic antibody against S. mutans, branded CaroRx, which it produces using transgenic tobacco plants. This product may be considered a therapeutic vaccine, applied once every several months, and is in Phase II clinical trials as of October 2007.[4]

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.

The filament delivery system is widely believed to be the reason this vaccine will succeed. The vaccine still needs a bit of tweaking before being implemented in humans, but other technologies are advancing to protect your teeth from cavities, including a genetically modified strain of Streptococcus mutans incapable of producing lactic acid that is currently in clinical trials.

Attempts using Replacement Therapy

On a different line of research, Dr. Jeffrey D. Hillman has developed a genetically modified strain of Streptococcus mutans which could be available in 2012-2013. The new strain, called BCS3-L1, is incapable of producing lactic acid, which 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.[5] BCS3-L1 colonizes the mouth and produces a small amount of a lantibiotic, called MU1140,[5] which allows it to out-compete S. mutans.[6]

Hillman suggests that treatment with BCS3-L1 in humans could also provide a lifetime of protection, or, at worst, require occasional re-applications. He figures the treatment would be available in dentists' offices and "will probably cost less than $100."[7] FDA Phase Ib clinical trials are to be held in 2008.[8] The product is being developed at Oragenics under license from the University of Florida. In April 2014 during an interview with The Wall Street Journal, Oragenics' CEO Dr. John Bonfiglio stated that the company has abandoned development of their S. Mutans Replacement Therapy (SMaRT), citing regulatory concerns and patent issues.[9]

The prospect of introducing genetically modified organisms into the human body's flora has raised muted concerns that have required additional study to address, including the prospect that BCS3-L1 might be more harmful than native S. mutans as a causative agent of inflammatory heart disease.[10] Whether this concern is among the open issues being investigated by Oragenics and the F.D.A. is not a subject open to public scrutiny.[11]

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.[12] 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 and when applied to a cavity, coming into contact with saliva causes the Peptide to assemble itself into fibers which form a scaffold or matrix in a cavity which attracts calcium, allowing the tooth to regenerate.[13][14] The Swiss based company Credentis has already licensed the peptide and finished early stage financing in February 2011[15]

DNA Vaccines

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.

Bacteriophage treatment

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.[16]

References

  1. ↑ "Panel on Caries Vaccine". National Institute of Dental and Craniofacial Research of the National Institute of Health. January 28, 2003. Retrieved 14 April 2008.
  2. ↑ Bowen, W.H. (December 1972). "Dental caries". Archives of Disease in Childhood 47 (256): 852. doi:10.1136/adc.47.256.849. PMC 1648396. PMID 4567073.
  3. ↑ Martin A. Taubman and 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. Retrieved October 7, 2007.
  4. ↑ "Planet Biotechnology Products". Planet Biotechnology.
  5. ↑ 5.0 5.1 "Replacement Theraphy". ONI Biopharma. Retrieved 6 January 2009.
  6. ↑ Hillman, Jeffrey D. (August 2002). "Genetically modified Streptococcus mutans for the prevention of dental caries". Antonie van Leeuwenhoek (Springer Netherlands) 82 (1-4): 361–366. doi:10.1023/A:1020695902160. PMID 12369203.
  7. ↑ "Genetically modified bacteria may prevent caries". HealthMantra. January 2002. Retrieved 2006-12-18.
  8. ↑ "Oragenics, Inc. Selects Qualia Clinical Services to Conduct SMaRT Phase 1 Trial". ONI Biopharma. Retrieved 6 January 2009.
  9. ↑ "Wall Street Journal Interview with Oragenics' CEO, Dr. John Bonfiglio - Transcript". April 2014. Retrieved 2014-05-01.
  10. ↑ "Wash that mouth out with bacteria!". Science News. 18 March 2000.
  11. ↑ Pollack, Andrew (30 November 2004). "Bacteria Enlisted for New Trials on Dental Health". New York Times.
  12. ↑ "Chewing gum with added bite". British Dental Journal 201 (5): 255. 2006. doi:10.1038/sj.bdj.4814014.
  13. ↑ "Breakthrough could make dental drills obsolete". Healthier Talk. 9 April 2011.
  14. ↑ S Kyle, A Aggeli, M J McPherson & E Ingham (2008). "THE SELF-ASSEMBLING PEPTIDE, P11-4 AS A SCAFFOLD FOR USE IN REGENERATIVE MEDICINE". European Cells and Materials 16 (3): 70. ISSN 1473-2262.
  15. ↑ "New Treatment Fixes Tooth Decay Without Drilling". Science Business. 24 August 2011.
  16. ↑ G. Bachrach, M. Leizerovici-Zigmond, A. Zlotkin, R. Naor and 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.