caries vaccine
{{short description|Vaccine protecting against tooth decay}}
{{Primary sources|date=April 2024}}
A caries vaccine is a vaccine to prevent and protect against tooth decay.{{cite web | url = http://www.nidcr.nih.gov/Research/ResearchPriorities/ExpertPanelsOnScientificOpportunities/PanelOnCariesVacine.htm | title = Panel on Caries Vaccine | publisher = National Institute of Dental and Craniofacial Research of the National Institute of Health | date = January 28, 2003 | accessdate = 14 April 2008 | archive-url = https://web.archive.org/web/20110929121725/http://www.nidcr.nih.gov/Research/ResearchPriorities/ExpertPanelsOnScientificOpportunities/PanelOnCariesVacine.htm | archive-date = 2011-09-29 | url-status = dead }} 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 since the 1970s. In 1972, a caries vaccine was said to be in animal testing in England, and that it would have begun human testing soon.{{cite journal | title=Dental caries | first=W.H. | last = Bowen | journal=Archives of Disease in Childhood |date=December 1972 | volume=47 | issue=256 | pages=849–53 | pmid=4567073 | pmc=1648396 | doi=10.1136/adc.47.256.849}} However, intrinsic difficulties in developing it, coupled with lack of strong economic interests, are the reasons why still no such vaccine is commercially available today.{{Citation needed|date=May 2023}} 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 young people.{{cite journal | title=Caries vaccine: A boom for public health. | first1= Chhabra| last1 = Richie | first2= Rajpal| last2 = Karan | journal= Annals of Tropical Medicine and Public Health |date=Jan 2016 | volume=9 | issue=1 | pages=1–3| doi=10.4103/1755-6783.168715| doi-broken-date= 1 November 2024| s2cid= 57200550| doi-access= free}}
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.{{cite journal | pmc = 414936 | title = Effects of Local Immunization with Streptococcus mutans on Induction of Salivary Immunoglobulin A Antibody and Experimental Dental Caries in Rats | journal = Infection and Immunity |date=June 1974 | volume = 9 | issue = 6 | pages = 1079–1091 |author1=Martin A. Taubman |author2=Daniel J. Smith | doi = 10.1128/IAI.9.6.1079-1091.1974 | pmid = 4545425}}{{Non-primary source needed|date=April 2024}}
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.{{Citation needed|date=April 2024}}
The International Associations 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.{{Cite journal |title=Second-generation Flagellin-rPAc Fusion Protein, KFD2-rPAc, Shows High Protective Efficacy against Dental Caries with Low Potential Side Effects |journal=Scientific Reports |volume=7 |issue=1 |pages=11191 |doi=10.1038/s41598-017-10247-8 |pmid=28894188 |pmc=5593867 |year=2017 |last1=Yang |first1=Jingyi |last2=Sun |first2=Ying |last3=Bao |first3=Rong |last4=Zhou |first4=Dihan |last5=Yang |first5=Yi |last6=Cao |first6=Yuan |last7=Yu |first7=Jie |last8=Zhao |first8=Bali |last9=Li |first9=Yaoming |last10=Yan |first10=Huimin |last11=Zhong |first11=Maohua |bibcode=2017NatSR...711191Y }}{{Non-primary source needed|date=April 2024}}
Attempts using replacement therapy
On a different line of research, Jeffrey Hillman from the University of Florida{{Cite web| title = This Germ Could Save Your Life| work = Popular Science| date = 31 January 2008| accessdate = 2016-09-20| url = http://www.popsci.com/scitech/article/2008-01/germ-could-save-your-life}} 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.{{cite web | url = http://www.oragenics.com/?q=about-us | title = Replacement Therapy | publisher = ONI Biopharma | accessdate = 6 January 2009}}{{Non-primary source needed|date=April 2024}} BCS3-L1 colonizes the mouth and produces a small amount of a lantibiotic, called MU1140, which allows it to out-compete S. mutans.{{cite journal | first = Jeffrey D. | last = Hillman | title = Genetically modified Streptococcus mutans for the prevention of dental caries | journal = Antonie van Leeuwenhoek |date=August 2002 | volume = 82 | pages = 361–366 | doi = 10.1023/A:1020695902160 | pmid = 12369203 | issue = 1–4| s2cid = 11066428 }} 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."{{cite web |url=http://www.healthmantra.com/ypb/jan2002/caries.htm |title=Genetically modified bacteria may prevent caries |publisher=HealthMantra |accessdate=2006-12-18 |date=January 2002}} The product was being developed by Oragenics, but was shelved in 2014, citing regulatory concerns and patent issues.{{cite web|url=http://www.oragenics.com/sites/default/files/wall_street_transcript_-_oragenics.pdf |title=Wall Street Journal Interview with Oragenics' CEO, Dr. John Bonfiglio - Transcript |accessdate=2014-05-01 |date=April 2014 |url-status=dead |archiveurl=https://web.archive.org/web/20140502004751/http://www.oragenics.com/sites/default/files/wall_street_transcript_-_oragenics.pdf |archivedate=2014-05-02 }}{{Non-primary source needed|date=April 2024}} In 2016, Oragenics received a 17-year patent for the product.{{cite web|title=Oragenics Receives New Patent for Improved Replacement Therapy for Dental Caries|url=http://www.oragenics.com/news-media/press-releases/detail/35/oragenics-receives-new-patent-for-improved-replacement|accessdate=8 January 2017}} In 2023, the startup Lumina Probiotic began developing a BCS3-L1 application in Próspera, Honduras.{{cite web |title=Oragenics Enters into Agreement with Lantern Bioworks for Replacement-Therapy Assets |url=https://www.oragenics.com/news-media/press-releases/detail/163/oragenics-enters-into-agreement-with-lantern-bioworks-for |date=September 29, 2003 |website=Oragenics |access-date=April 13, 2025}}
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.{{cite journal | url = http://www.thefreelibrary.com/Wash+that+mouth+out+with+bacteria!-a061793406 | title = Wash that mouth out with bacteria! | journal = Science News |date=18 March 2000}}
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.{{cite journal | title = Chewing gum with added bite | journal = British Dental Journal | year =2006 | volume = 201 | page = 255 | issue = 5 | doi = 10.1038/sj.bdj.4814014| doi-access = free }} 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.{{Citation needed|date=April 2024}}
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.{{cite journal | url = http://www.healthiertalk.com/breakthrough-could-make-dental-drills-obsolete-4611 | title = Breakthrough could make dental drills obsolete | journal = Healthier Talk | date = 9 April 2011 | access-date = 27 May 2013 | archive-date = 17 August 2016 | archive-url = https://web.archive.org/web/20160817005044/https://healthiertalk.com/breakthrough-could-make-dental-drills-obsolete-4611/ | url-status = dead }}{{cite journal |url=http://www.ecmjournal.org/journal/supplements/vol016supp03/pdf/v016supp03a070.pdf |author1=S Kyle |author2=A Aggeli |author3=M J McPherson |author4=E Ingham |title=The Self-Assembling Peptide, P11-4 As a Scaffold for Use in Regenerative Medicine |journal=European Cells & Materials |volume=16 |issue=3 |pages=70 |year=2008 |issn=1473-2262 |access-date=2013-05-27 |archive-date=2016-03-04 |archive-url=https://web.archive.org/web/20160304103145/http://www.ecmjournal.org/journal/supplements/vol016supp03/pdf/v016supp03a070.pdf |url-status=dead }} The Swiss-based company Credentis has licensed the peptide and launched a product called Curodont Repair in 2013.{{cite journal | url = http://sciencebusiness.technewslit.com/?p=5748 | title = New Treatment Fixes Tooth Decay Without Drilling | journal = Science Business | date=24 August 2011}} Recent studies show a positive clinical effect.{{cite journal | title = Klinischer Effekt biomimetischer Mineralisation bei Approximalkaries | journal = Stomatologie | date=19 July 2014 | doi=10.1007/s00715-014-0335-4 | volume=111 | issue = 4–5 | pages=175–181|last1 = Schlee|first1 = M.| last2 = Rathe | first2 = F. | last3 = Huck | first3 = T. | last4 = Schad | first4 = T. | last5 = Koch | first5 = J.H. | last6 = Tjaden | first6 = A. | last7 = Bommer | first7 = C. | doi-access = free }}{{Non-primary source needed|date=April 2024}}
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. Some believe that the rational target for developing an anti-caries vaccine is a protein antigen, which has adherent functional and important immunogenic regions.{{Cite journal|last1=Guo|first1=JH|last2=Jia|first2=R|last3=Fan|first3=MW|last4=Bian|first4=Z|last5=Chen|first5=Z|last6=Peng|first6=B|date=Mar 2004|title=Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans|pmid=14981132|journal=Journal of Dental Research|volume=83|issue=3|pages=266–270|doi=10.1177/154405910408300316|s2cid=46360161}}{{clarify|date=August 2021}}{{Non-primary source needed|date=April 2024}}
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.{{cite journal |author1=G. Bachrach |author2=M. Leizerovici-Zigmond |author3=A. Zlotkin |author4=R. Naor |author5=D. Steinberg |title=Bacteriophage isolation from human saliva |journal=Letters in Applied Microbiology |volume=36 |issue=1 |pages=50–53 |date=December 2002 |pmid= 12485342|doi=10.1046/j.1472-765X.2003.01262.x|s2cid=34349845 |doi-access=free }}{{Non-primary source needed|date=April 2024}}
References
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{{Vaccines}}
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