Dental caries (tooth decay or cavities) is the most common non-communicable disease (NCDs) worldwide. It is chronic and strongly socially patterned as with most NCDs. Children living in poverty, and socially marginalized groups are the most affected by dental caries, and have poor access to dental care. [1] The Global Oral Health Status Report (GOHSR) published by the World Health Organization (WHO) estimates untreated dental caries (both deciduous and permanent teeth) as one of the leading causes of oral disease burden. [2] In some high-income countries, dental caries is among the main reasons for hospitalization of children. Severe dental caries is a frequent cause of absenteeism at school or work. [3]
Dental caries is a multifactorial disease influenced by host, agent, and environmental factors. The four components of dental caries are:
Susceptible host
Cariogenic flora
Suitable substrate
Sufficient length of time
The primary etiologic agents are Streptococcus mutans, Streptococcus sobrinus, and Lactobacillus. S. mutans initially attaches to the tooth via the interaction of bacterial proteins with lecithin in the dental pellicle (a thin coating layer of high tenacity covering all solid surfaces in the oral cavity, composed of proteins and glycoproteins).
Streptococcal adhesins, (facilitate adherence to substrates present in their natural environment within the mammalian host) in S. mutans bind to the tooth pellicle. They secrete glucosyltransferases, GTF (polysaccharide containing glucose, rhamnose, and sometimes galactose and galactosamine), favoring the accumulation of more bacteria through interactions with bacterial cell-associated glucan-binding proteins, GBP. These bacteria then metabolize and release lactic acid, demineralizing the enamel and causing dental caries. [4]
The true burden and impact of dental caries are often underestimated, leading to inadequate prioritization in health planning. Current interventions typically focus on isolated disease treatment and costly clinical procedures. But it should move towards integrated, cost-effective public health strategies that address entire populations and target common risk factors for NCDs. It is crucial to ensure that population-wide preventive interventions are universally available and accessible.
Some of the policies and programs aimed at reducing dental caries as part of broader efforts to prevent NCDs are: [3]
Taxing sugar-sweetened beverages and foods high in free sugar content
Implementing clear nutrition labeling, particularly regarding sugar content
Regulating the marketing and advertising of high-sugar foods and beverages to children
Enhancing the food environment in public institutions, especially schools, by regulating the sale of high-sugar foods and beverages
Prioritizing awareness and access to clean water as a safe and tooth-friendly drink
Promoting the use of fluoride - community water fluoridation, professional application of fluoride varnish, gels or foams, fluoride-containing products like toothpaste, mouthwashes and dietary fluoride supplements [5]
The use of fluoride through water fluoridation has been implemented by few countries to reduce the prevalence of dental caries, and has been found that it plays a significant role in caries reduction. But, it has been controversial due to ethical and public health issues. I feel that reductions in starch and sugar consumption are unlikely to reduce caries rates because of differences in socioeconomic status, especially in developing countries. The preventive measures, such as fluoride treatments or good oral hygiene practices, requires ongoing maintenance and monitoring, which isn't possible when considering masses.
Dr. G. Sneha, General Dentist, Chennai, India
The factors responsible for maintaining oral health are
Integrity of the mucosa
Saliva
Gingival crevicular fluid
Humoral and cellular immune components [6]
A notable feature of the tooth surface is its influence by both local salivary and systemic immune mechanisms. The division between these two immune mechanisms occurs near the gingival (gum) margin. This is unique as it is the only site in the body where an interface exists between secretory and systemic immune mechanisms. Bacteria on the tooth surface may be affected by two types of antibodies: secretory (salivary) antibodies (sIgA) and serum antibodies (IgG, IgM, and IgA), which enter the mouth via the gingival crevice.
The cellular immune response (activation of phagocytes, T-lymphocytes, and the release of various cytokines in response to an antigen) does not play a direct role in the immunology of dental caries. T-cells modify the humoral immune response (mediated by antibody molecules) through their helper and suppressor actions. They also cause inflammation of the gingival tissues, which increases the flow of gingival fluid and thus facilitates the access of IgA and polymorphonuclear leukocytes (PMNLs) to the mouth. [6]
Dental caries is an irreversible microbial disease of the tooth that aligns with the concept of an infectious disease. This prompts the consideration of vaccination possibilities for dental caries. For the development of a vaccine against dental caries, several factors must be considered.
The vaccine needs to be safe for human use
The vaccine must contain the appropriate virulence antigen(s) of S. mutans that induce antibodies to prevent the bacterium from causing disease
The vaccine must be administered through the proper route to induce the desired immune response
The vaccine composition must be effective in reaching immune inductive sites.
The vaccine should be cost-effective for widespread application.
Immune interventions can be applied at various stages of caries pathogenesis. One approach involves eliminating microorganisms in the salivary phase before they can colonize, which can be achieved by enhancing the antimicrobial activity of salivary IgA antibodies. Dental caries vaccines are developed to target the antigenic components of S. mutans, such as adhesins, GTF, GBP and dextranases.
Initially, the most common type of dental caries vaccine was developed from whole cells of killed S. mutans, which were used as antigens. Since S. mutans contains heart cross-reactive antigens (HCRA), these whole-cell vaccines were unsuitable for parenteral use and had to be administered orally.
Mucosal vaccine system
Secretory IgA (sIgA) is a major immune component in the secretions of major and minor salivary glands. The tooth surfaces are continually soaked by saliva in which this principal immunoglobulin is present. Mucosal applications of dental caries vaccines are generally preferred for inducing sIgA antibodies. This would provide the first line of defense against the colonization of these bacteria on tooth surfaces.
Oral administration of S. mutans antigens in various forms, such as through drinking water, capsules, and liposomes, significantly reduces caries and increases salivary IgA antibody levels in animal studies. Intranasal delivery of S. mutans antigens induces protective immunity against cariogenic streptococci by targeting nasal-associated lymphoid tissue (NALT). Topical application of S. sobrinus antigens to the tonsils of rabbits induces an immune response, reducing cariogenic infections and increasing IgA-producing cells in salivary glands.
Labial application (minor salivary gland) of S. sobrinus GTF significantly reduced S. mutans colonization in the oral flora following dental prophylaxis. Rectal immunization with non-oral bacterial antigens like Helicobacter pylori induced sIgA antibodies in distant salivary sites, suggesting potential for salivary IgA response to GTF. Subcutaneous administration of killed S. mutans in monkeys induced serum IgG, IgM, and IgA antibodies, which protected against dental caries through gingival crevicular fluid. Administering antigens via the gingival crevicular fluid increased local IgG and IgA levels, with varying success depending on the method and type of antigen used. [6]
Passive immunization
Application of murine monoclonal IgG antibodies specific for S. mutans antigens to monkey gingiva decreased S. mutans colonization and prevented dental caries over a year. Hens were immunized with GTF antigens to produce egg yolks enriched with IgG antibodies. Experimental use of these antibodies reduced dental caries in rodents by 50%. Systemic immunization of cows with a vaccine from whole S. mutans cells produced IgG antibodies in serum and milk whey. Preliminary human trials using a bovine milk whey mouth rinse containing antibodies to S. mutans showed reduced S. mutans compared to controls after 14 days of use. Secretory IgA has been produced by crossbreeding four tobacco plants, resulting in a colorless and tasteless vaccine. This antibody, effective against S. mutans, can be painted onto teeth and is the first plant-derived vaccine. [6]
Active immunization
One method is ingestion of whole S. mutans in capsule form which do not release contents until reaching Peyer's patches, stimulating an antibody response. Synthetic peptides from GTF enzyme as oral vaccine in rats inhibits enzyme function effectively. S. mutans antigens coupled to Cholera toxin subunits induce excellent immune response and suppresses S. mutans colonization, reducing caries. S. mutans genes fused to virulent Salmonella is another method. Attenuated salmonella serves as an effective vaccine technique. [6]
At birth, the human gastrointestinal tract including the oral cavity is sterile. But it quickly becomes exposed to microbes. The oral cavity is first colonized by bacteria such as S. salivarius. When teeth emerge (4-8 months), bacteria like S. sanguis and S. mutans colonize. If children do not acquire S. mutans by a median age of 26 months, then their primary teeth are unlikely to be colonized by them. This period, from tooth emergence to the closure of 'window of infectivity', is vital for determining oral microbial colonization. Infants can develop salivary IgA antibodies even before teeth emerge. Thus, immunizing children with a dental caries vaccine before this window closes is crucial. Studies in this age group are essential for evaluating vaccine potential. [7]
Concerns arise about using S. mutans for vaccine development due to reports of rabbits hyper-immunized with this bacterium developing antibodies that cross-reacted with human heart tissue (HRAC). This concern was attributed to the Ag I/II of S. mutans, which was thought to cause this cross-reactivity. However, subsequent research disproved this hypothesis.
No infants have yet received a mutans streptococcal vaccine. There have been no adverse effects noted in adult volunteers who were given mucosal immunization (oral/nasal route) with a potential caries vaccine. Since S. mutans are part of the native oral microflora, adverse effects from immunization with antigenic components of this bacterium are unlikely. [7]
Candidate vaccine antigens are rigorously tested for tolerability, and any concerns for vaccine development can be eliminated using modern tools in molecular biology. It is also crucial to explore alternative vaccination methods, including: [7]
Purifying candidate antigens to create a subunit vaccine
Using recombinant DNA techniques to insert virulence factors from cariogenic organisms into a non-cariogenic, non-cross-reactive bacterium. DNA vaccine approaches for dental caries have had a history of success in animal models.
Studies have shown possible problems using Streptococcus mutans as an immunogen in vaccine can lead to the production of heart reactive antibody (cross reactivity). This poses a major concern. Dental researches are now working towards it. There can also be cases of hypersensitivity and also clinical trials have been concentrated only on S. mutans, so chances are there for ineffectiveness as caries is caused by wide range of bacteria.
Dr. G. Sneha, General Dentist, Chennai, India
None of the dental caries vaccines have yet been introduced to the market. There are challenges in eliciting and sustaining elevated levels of antibodies in oral fluids which need to be rectified with further studies. [8] Despite the compelling need for a vaccine and the promising vaccine candidates identified through animal studies, there is limited conduct of larger-scale trials.
Currently, we don't have any commercially available vaccine for caries. Despite many years of promising animal studies, clinical trials and research we haven't still been able to launch a caries vaccine. I think we are close to having a option, but intrinsic difficulties has hampered its development.
Dr. G. Sneha, General Dentist, Chennai, India
The main reason extensive studies are not prioritized is because dental caries is seen as non-life-threatening disease. However, it's important to note that even though dental caries don't directly endanger life, they have serious consequences like pain, disfigurement, and reduced productivity, particularly affecting disadvantaged children. Additionally, there's a potential link between S. mutans and fatal infectious endocarditis. [9]
Those against dental caries vaccination believe that the risks of vaccinating healthy individuals for a non-life-threatening condition may not be worth it. Developing a vaccine for dental caries requires significant resources. The dental community is concerned that if other preventive approaches are adequately funded, then that might also effectively address dental caries. However, resolving these concerns require well-designed clinical trials. Clinical immunological science is essential for guiding public decisions about the usefulness of a dental caries vaccine. [9]
Dental caries, being an infectious disease, necessitates the development of an effective vaccine capable of inducing a mucosal immune response to significantly reduce its prevalence worldwide. It's important to note that while a vaccine against dental caries would complement existing preventive measures such as good oral hygiene, proper nutrition, and the use of sealants, fluoride, and chlorhexidine, it would offer an additional layer of protection for the global population.
Both preclinical and clinical studies conducted in adults have provided valuable insights into the safe and effective use of a mucosal vaccine for preventing dental caries. However, further research in infants and children, who are the target population, is essential to determine the vaccine's tolerability and efficacy. [9]
People must know that the field of dentistry has been undergoing a lot of research and development, and the caries vaccine production will prove as a turning point in the field. Most of the general public don't know that something like vaccine is under process for caries prevention. I feel that caries vaccination will have a life changing impact on public health, it will significantly help in improving dental health of the masses. Firstly, it has the potential to provide long-lasting protection against dental caries. Vaccines provide a single dose of protection that can last for years or even a lifetime, unlike other methods of caries protection which require constant monitoring. Caries vaccination will be the cost-effective way to prevent dental caries. Hence, this is a more feasible option.
Dr. G. Sneha, General Dentist, Chennai, India
Considering the development of the mucosal immune system and the critical "window of infectivity," the optimal timing for immunization to confer protection against dental caries is likely between 6 and 18 months of age. Additionally, administering a booster dose of the mucosal caries vaccine in children when they transition to permanent dentition should offer long-term protection. Clinical trials are underway to evaluate the protective effects of a mucosal anticaries vaccine in children, and the outcomes of these studies are eagerly anticipated.
Moving forward, integrating a dental caries vaccine into public health strategies could significantly reduce this preventable disease. It would also ease pain and disfigurement and improve quality of life, especially for disadvantaged groups. Developing this vaccine is both a scientific goal and an ethical commitment to social justice. This ensures all children, regardless of socio-economic background, have an equal chance for good oral health.
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