The search for a single organism as the cause for dental caries began shortly after the recognition of the role of bacteria in the etiology of caries. Clarke in 1924 isolated an organism which he named as streptococcus mutans.
Evidence rapidly accumulated that streptococcus mutans was the major causative organism along with lactobacilli and S.milleri (specific immune defence against the mutans streptococci depends on salivary antibodies). At the same time, Herman isolated and characterised immunoglobulin A (IgA) and shortly thereafter Tomasi identified the secretory form of IgA in external biological fluids including saliva. This discovery not only provided insight into the specific immune factors that mediate host defence at mucosal surfaces but also suggested to the dental researchers in the early 1970’s that it may be possible to prevent dental caries by inducing salivary IgA antibodies against mutans streptococci.
Immunity :-
Immunity refers to the resistance exhibited by the host towards injury caused by microorganism and their products.
Types:
I) Innate -Non-specific
-Specific
II) Acquired:
Active: – natural
– artificial
Passive: – natural
– artificial
Vaccine: A vaccine is a preparation that induces artificial immunity.
Types:
1) Bacterial
e.g. (a) Live: BCG for TB
(b) Killed: TAB for enteric fever
2) Viral
e.g (a) Live: Oral poliomyelitis vaccine
(b) Killed: Salk vaccine for poliomyelitis
3) Bacterial products
e.g. Toxoids for diphtheria
Vaccines are given at different ages to boost the body’s immune system and to provide protection against various diseases :-
Immunology of Dental Caries :
Role of secretory IgA:
IgA is a component of saliva, breast milk, colostrum and secretion that bathes the mucosal surfaces.
1. M cells lining the Peyer’s patches sample and process the mucosal antigens.
2. These cells present the antigenic determinants to B and T lymphocyte that leave the peyer’s patch and travel through circulation and lymphatics.
3. The B lymphocyte differentiate to plasma cells which synthesize and secrete specific SIgA antibodies against S.mutans into mucosal fluid.
Mode of Action :
•Neutralization of the microbial enzyme, toxins.
•Inhibition of attachment, colonization and penetration of antigen into mucosa.
•Opsonization and activation of the alternate complement pathway.
Role of Streptococcus mutans :
Virulence factors of S.mutans :-
The properties of an organism responsible for its pathogenicity are called virulence factors. With S. Mutans, the most prominent features are:
1. Ability to form acid rapidly from dietary carbohydrates .
2. Ability to tolerate acid conditions.
3. Ability to synthesize an insoluble extracellular polysaccharide (dextran) from sucrose which helps the organism to become attached to the teeth .
These properties are probably the most important features of S. Mutans giving rise to its virulence.
The cell surface of S.mutans possess many antigens
1) Glucosyl transferases (GTF):
At least 2 types of GTF’s are known to exist – GTF I and GTF II. The primary function of GTF is synthesis of water insoluble glucans.
2) Surface protein antigens:
These are large protein molecules (160-180 KD) which are cell surface proteins and immunologically related to dextranase. The main function of these proteins appears to be sucrose independent adherence to the hydroxyapatite surface.
3) Dextranases: These are large protein enzymes (160-175 KD) which break polymers of glucose into dextrans. These enzymes are probably used by oral streptococci to modify glucan products
4) Glucans: These are tree-like homopolymers of glucose featuring many branches. There are 2 types of glucans viz.
(a) Water soluble
(b) Water insoluble
These two products are qualitatively and quantitatively different.
Glucans act as molecular barriers, retain water and although they do not play a role in initial colonization. they greatly help in the adhesion of micro organisms to the tooth surface.
5) Lipoteichoic acid: These are molecules found in Gram+ve bacteria and are in some ways analogous to the lipopolysaccharides of Gram-ve bacteria. The exact role in caries pathogenesis is not clear but this may propagate adhesin by surface interactions.
6) Adhesin I/II: A group of non-fibrillar proteins responsible for initial adherence to tooth surface. they have the ability to bind to collagen of dentinal tubules and contribute to progression of dental caries. This characteristic of Ag / support its potential as vaccine candidate.
Strategies of Immunization for Dental Caries :-
1. Induction of the common mucosal immune system.
2. Induction of the systemic immune system.
3. Passive immunization with topical application of antibodies to the tooth surface.
1. Common mucosal immune system (CMIS) :-
Induction of common mucosal immune system by oral immunization stimulates specific immunoglobulin A(IgA) antibodies in all secretions including saliva. CMIS has the advantage of inducing antibodies only in saliva (not in serum)that have intimate contact with S.mutans on tooth surface. CMIS can be induced by oral,nasal and topical routes.
2. Systemic immunization :
Intramuscular or subcutaneous injection induces only serum antibodies. These serum antibodies come in contact with the tooth surface only via exudation into the gingival crevicular fluid and protection may not extend significantly above the gingival margin. Parenteral immunization directed against S.mutans could favour the establishment of a noncariogenic microflora on teeth. Such flora could prevent or delay colonization of pathogenic S.mutans.
3. Passive immunization :
It utilises previously synthesized antibodies to prevent disease, instead of stimulating an individual to produce new antibodies by immunization.
Strategies include development of antibodies to mutans streptococcal antigens in cow’s milk and hen’s egg and the genetic engineering of human-like S-IgA antibodies in plants.
Timing and Target Population:
Caufield (1996) stated that there is a window of infectivity between 19-33 months during which teeth get infected with S.mutans. It has been suggested that the most beneficial time for vaccination against dental caries would be in infancy prior to eruption of teeth. This would promote the induction of adherence inhibiting salivary IgA thus delaying colonization of S.mutans.
With the establishment of early colonizers there would be a synergistic effect of suppressing the colonization of S.mutans during the time span of window of infectivity. A booster dose of vaccination may be required at the time of eruption of first permanent molars.
Advantages
1. As the vaccine would be administered before the deciduous dentition has erupted (at about 6 months of agel, it would prevent development of disease in children who show the greatest incidence of caries
2.The public is well disposed to vaccination and the caries vaccine could be given at the same time as vaccines against diphtheria and tetanus.
3.As individuals, parents can decide whether to have their child vaccinated.
4.Immunity could be boosted thereafter at intervals, to provide life-long protection.
5.Existing delivery systems of immunization can be used without any additional financial burden being incurred.
Limitations :
1. Streptococcus mutans is only partially responsible for dental caries. Consequently, an S. mutans vaccine would provide partial protection.
2. S. mutans is acquired during infancy and generally remains in the oral cavity for life. Therefore, the immune system must respond to the bacteria on a daily basis, not on a periodic basis.
3. Dental caries is a disease process, which develops on the hard tissue of the tooth. The formation of a lesion involves destruction of tissue, but does not bring the organism into contact with the immune system and consequently there is no stimulation of immunoglobulin synthesis.
4. An antibody may even promote back adherence by bonding to the tooth. This mechanism might explain why immunization could also cause an increase in caries incidence.
Current Status of Caries Vaccine :
Current information suggests that the general clinical use of a dental caries vaccine is several decades away from reality. There are a number of reasons for this:
1. As dental caries is not directly life threatening, the Food and Drug Administration. (FDA) is likely to spend a significant amount of time studying any caries vaccine extremely closely before granting it approval.
2. The need for a caries vaccine could change because of the fluctuating demographics of the disease pattern in the pediatric population (i.e., there are more caries free children, but those who have caries have significant number of lesions).
However, there is still a need for this vaccine in several selected populations:
(a) Extremely caries active children and adults who do not respond to conventional treatment. (i.e rampant caries)
(b) Immuno compromised patients such as patients who have received organ transplants, radiation therapy patients, patients suffering from xerostomia and Sjogren’s syndrome, Acquired Immuno deficiency Syndrome – patients as well as individuals on long term antibiotic or antifungal therapy.
(c) Individuals in developing countries who do not have access to fluoride treatment or regular dental care.