Caries Vaccine
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A caries vaccine is a
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
to prevent and protect against
tooth decay Tooth decay, also known as cavities or caries, is the breakdown of teeth due to acids produced by bacteria. The cavities may be a number of different colors from yellow to black. Symptoms may include pain and difficulty with eating. Complicatio ...
. ''
Streptococcus mutans ''Streptococcus mutans'' is a facultatively anaerobic, gram-positive coccus (round bacterium) commonly found in the human oral cavity and is a significant contributor to tooth decay. It is part of the " streptococci" (plural, non-italic lowercase ...
'' (''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. 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. 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.


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 An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
production. Planet Biotechnology developed a
monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...
against ''S. mutans'', branded CaroRx, produced with
transgenic A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...
tobacco plants. It is a
therapeutic vaccine A therapeutic vaccine is a vaccine which is administered after a disease or infection has already occurred. A therapeutic vaccine works by activating the immune system of a patient to fight an infection. A therapeutic vaccine differs from a prophyla ...
, applied once every several months. Phase II
clinical trials Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
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 In biology, a protein filament is a long chain of protein monomers, such as those found in hair, muscle, or in flagella. Protein filaments form together to make the cytoskeleton of the cell. They are often bundled together to provide support, st ...
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.


Attempts using replacement therapy

On a different line of research, Jeffrey Hillman from the
University of Florida The University of Florida (Florida or UF) is a public land-grant research university in Gainesville, Florida. It is a senior member of the State University System of Florida, traces its origins to 1853, and has operated continuously on its ...
developed a genetically modified strain of ''Streptococcus mutans'' called BCS3-L1, that is incapable of producing
lactic acid Lactic acid is an organic acid. It has a molecular formula . It is white in the solid state and it is miscible with water. When in the dissolved state, it forms a colorless solution. Production includes both artificial synthesis as well as natu ...
– the acid that dissolves
tooth enamel Tooth enamel is one of the four major Tissue (biology), tissues that make up the tooth in humans and many other animals, including some species of fish. It makes up the normally visible part of the tooth, covering the Crown (tooth), crown. The ...
– and aggressively replaces native flora. In laboratory tests, rats who were given BCS3-L1 were conferred with a lifetime of protection against ''S. mutans''. BCS3-L1 colonizes the mouth and produces a small amount of a
lantibiotic Lantibiotics are a class of polycyclic peptide antibiotics that contain the characteristic thioether amino acids lanthionine or methyllanthionine, as well as the unsaturated amino acids dehydroalanine, and 2-aminoisobutyric acid. They belong to ...
, called MU1140, which allows it to out-compete ''S. mutans''. 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." The product was being developed b
Oragenics
but was shelved in 2014, citing regulatory concerns and patent issues. In 2016, Oragenics received a 17-year patent for the product. 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. Another approach is being pursued by
BASF BASF Societas Europaea, SE () is a German multinational corporation, multinational chemical company and the List of largest chemical producers, largest chemical producer in the world. Its headquarters is located in Ludwigshafen, Germany. The ...
, focused on replacing native
lactobacillus ''Lactobacillus'' is a genus of Gram-positive, aerotolerant anaerobes or microaerophilic, rod-shaped, non-spore-forming bacteria. Until 2020, the genus ''Lactobacillus'' comprised over 260 phylogenetically, ecologically, and metabolically diver ...
flora with a variety dubbed ''L. anti-caries'', which prevents ''S. mutans'' from binding to enamel. 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 , mottoeng = And knowledge will be increased , established = 1831 – Leeds School of Medicine1874 – Yorkshire College of Science1884 - Yorkshire College1887 – affiliated to the federal Victoria University1904 – 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. The Swiss-based company Credentis has licensed the peptide and launched a product called Curodont Repair in 2013. Recent studies show a positive clinical effect.


DNA vaccines

DNA vaccine A DNA vaccine is a type of vaccine that transfects a specific antigen-coding DNA sequence into the cells of an organism as a mechanism to induce an immune response. DNA vaccines work by injecting genetically engineered plasmid containing the ...
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.


Bacteriophage treatment

The use of ''
Enterococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D ''Streptococcus'' system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus ''Enterococcus'', ''E ...
'' bacteriophages as a form of treatment for caries has been considered, as they are capable of maintaining persistent stability in human saliva.


References

{{DEFAULTSORT:Caries Vaccine Vaccines Dentistry Tooth decay