Dental caries is one of the most common irreversible diseases of the tooth structure where a wide group of microorganisms are responsible as they are the main etiologic bacteria. To reduce the incidence and prevalence of dental caries, various modalities have been adopted over the years by modifying various etiologic factors. One of the latest advances is caries vaccine that involves the application of advanced genetic technique by modifying Streptococcus mutans (S. mutans) and using it as a dental vaccine. This review article highlights the mechanism and prospects for dental caries vaccine that in the times ahead will be a blessing for health care providers.
Keywords: Caries vaccine, dental caries, Streptococcus mutans (S. mutans)
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Chhabra R, Rajpal K. Caries vaccine: A boom for public health. Ann Trop Med Public Health 2016;9:1-3
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Chhabra R, Rajpal K. Caries vaccine: A boom for public health. Ann Trop Med Public Health [serial online] 2016 [cited 2020 Sep 18];9:1-3. Available from: https://www.atmph.org/text.asp?2016/9/1/1/168715
Dental caries is defined as an irreversible disease of the calcified tissues of the teeth that occurs due to complex interaction between the host, acid-producing bacteria, and carbohydrates.  Although it is not life-threatening, it is still a major problem for health care providers. In this modern scenario, it is no less than an epidemiological disease. A wide group of microorganisms, including Streptococcus mutans (S. mutans), Lactobacillus acidophilus, Lactobacillus fermentum, and Actinomyces viscosus,  is responsible for causing this dental disease. These microorganisms are the main etiologic bacteria behind dental caries. These bacteria on interaction with sugar present in the diet produce lactic acid that results in dental caries. S. mutans is the most prevalent species among all the microorganisms as a causative organism of dental caries.
Various modalities have been adopted and tested to prevent and cure this disease by modifying or treating the host substrate or host bacteria. These include the use of mechanical removal of plaque by tooth brushing and flossing and by chemical methods such as the use of antiplaque agents, pit and fissure sealants, and fluoride application. Most of these strategies are effective but none of these methods reduce the susceptibility of the host to get affected by dental caries. Therefore, it requires the need to look for an alternative approach that aims at combating this disease at both homecare and professional setups.
One such latest approach for the prevention of dental caries is caries vaccine. The application of this advanced genetic technique could prove to be substantial in preventing common infectious disease. Moreover, vaccines can be well-suited for public health applications, especially for those who cannot render regular dental care. This technique of vaccination will prevent or diminish the impact of dental caries, particularly in the younger age group.
Injected vaccines containing lactobacilli were administered with limited success in the 1940s. At that time, the molecular pathogenesis of S. mutans was unknown and an appropriate understanding of the oral environment was not established.  Most virulence characteristics were unclear, with the exception of the ability of cariogenic bacteria to produce enamel-dissolving acid.
“Window of infectivity” is the time period when S. mutans shows more colonization in children. The oral immune system undergoes a rapid development with the secretory immunoglobulin A (IgA) antibody being secreted in the saliva at 1 month of age.  Within weeks of the initial exposure to S. mutans, the mucosal IgA is secreted. The infant’s saliva contains the immunoglobulin M (IgM) and IgA1 isotypes in the first month of life and by 6-9 months of age, the saliva is similar to an adult’s saliva in composition. The initial adherence of S. mutans to the tooth is through interaction of the bacterial protein with lecithin in the dental pellicle. The streptococcal adhesins present in S. mutans bind to the tooth pellicle followed by the secretion of glucosyltransferases (GTFs) that help in the accumulation of a large number of S. mutans. It occurs due to an interaction with the bacterial cell-associated glucan-binding proteins. Lactic acid is released by the metabolism of S. mutans that leads to demineralization of the enamel, thus causing dental caries. 
Mechanism of dental caries vaccine
Adaptive immunity is imparted by secretory IgA in the saliva apart from other immunoglobulins such as IgG and IgM. IgG and IgM are present in the saliva from gingival circular fluid.  Lymphocytes, macrophages, and neutrophils are also present in the saliva.
Mechanisms by which salivary IgA antibodies act against S. mutans are the following: 
- The salivary IgA may act as a specific agglutinin with the bacterial surface receptors and inhibiting colonization and subsequent caries formation. Also, inactivation of the surface GTF by interference with one or more of the functional activities of the enzyme can lead to decreased plaque formation.
- The migration of antigen-sensitized IgA precursor B cells from the gut-associated lymphoid tissues (GALTs) to the salivary glands. The GALTs and solitary lymphoid nodules, especially Peyer’s patches, and are a rich source of precursor IgA B cells that have the potential to populate distant lymphoid tissues; and the salivary glands can inhibit the activity of GTF.
The humoral and cellular components of the systemic immune system are also present at the gingival crevicular level that may protect the tooth surface as well.
Antigenic components of S. mutans targeted by vaccine
The antigenecity of S. mutans is due to the adhesives present within its structure. These single polypeptide chains are approximately 1,600 residues in length. S. mutans antigen (Ag) I/II contains an alanine-rich tandem-repeating region in the N-terminal third and a proline-rich repeat region at the center of the molecule that are associated with the adhesin activity of Ag I/II. Immunological approaches support the adhesin-related function of the Ag I/II family of proteins and its repeating regions.
S. mutans that have lost the ability to produce GTF are unable to produce disease in animal models. S. mutans has the following three forms of GTFs: GTF-1, GTF-S-1, and GTF-S and the respective genes are GTF-B, GTF-C, and GTF-D. Antibodies directed to native GTF or sequences associated with its catalytic- or glucan-binding function interfere with the synthetic activity of the enzyme and with in vitro plaque formation.  Since GTFs from the two major cariogenic streptococcal species in humans, i.e., S. mutans and S. sobrinus, have very similar sequences in the functional domains, immunization with GTF protein or subunit vaccines from one species can induce a measure of protection for other species.
S. mutans destroys dextran by producing the enzyme dextranase so that the bacterium can easily invade dextran-rich early dental plaque. If dextranase is used as an agent, it can prevent colonization of the organism in early dental plaque.
Routes of administration 
There are various routes of administration of these dental vaccines, namely, oral, intranasal, tonsillar, and rectal routes and through the minor salivary glands, the gingival route, and the systemic route.
Prospects and concerns regarding the use of caries vaccine
Vaccine therapy is done with the objective of preventing infection, i.e., immunization before infection. As the association of S. mutans is seen as early as the 34th day in the mouth of the child, immunization for dental caries should begin as early as in the second year of life for people with more risks of infection.  If bacterial colonization of the dental biofilm is complete after eruption of all primary teeth, and if one can, through immunization, prevent S. mutans colonization prior to this period, the benefit of early immunization might extend until the secondary teeth begin to erupt, exposing new ecological conditions. Subsequent immunization could then be initiated. Clearly, several possible dental caries vaccine approaches may have application in pediatric clinical trials. Several components of S. mutans have been shown to protect in animal model systems. Protective epitopes of these components continue to be identified and incorporated into designs to increase their protective value. Several routes of administration can induce protective immune responses, at least in the model systems. Also, significant progress is being made in the adjuvant field to remove the toxic properties of powerful mucosal adjuvants while maintaining their adjuvant properties. Animate (attenuated bacterial vectors) and inanimate (liposomes and microparticles) delivery systems have been identified to provide more efficient targeting of the vaccine. Both passive and active immunization approaches have demonstrated success in animal models and human clinical trials. With all these apparently effective preclinical approaches one may ask, “What is the ideal dental caries vaccine approach?” Ideally, one would favor a vaccine that gives the broadest coverage to intercept infection by all common cariogenic S. mutans strains, one that would work for both low- and high-risk populations, the immunity of which would last through the critical primary and secondary infection periods, one that could be given with or as part of other immunizations, one that could be given through various routes and still be effective, one that would be inexpensive, one that could be delivered by individuals with little training, and one that might provide secondary immunity  to others who were themselves not immunized in the population.
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Conflicts of interest
There are no conflicts of interest.
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