DENTAL

CARIES

VACCINE

Dr. R. Venkitachalam,

PG I year, Department of Public Health Dentistry, Amrita School of Dentistry

Learning objectives

How immune system works

The need for caries vaccine in public health

point of view

Methods of caries vaccine administration

CONTENTS

Introduction

Immunity

Need for caries vaccine

Microbiology of dental caries

Routes of administration

Advantages

Disadvantages

Passive immunization

Public Health perspective

Summary

References

INTRODUCTION

Definition: Dental caries is an infectious microbiological disease of the teeth that results in localized dissolution and destruction of the calcified tissue. It is one of the most common diseases in humans.

Dental caries is a major public health problem.

Vaccine: An immunobiological substance designed to produce a specific protection against a given disease.

IMMUNITY

It is defined as resistance exhibited by the host against any foreign antigen includingmicroorganisms.

Classification - ??

Classification of immunity

IMMUNITY

Innate

Skin, tears, low pH of stomach, respiratory cilia,

normal flora of gut

Acquired

Natural

Natural active

During exposure to disease ,

antibobies are produced

Natural passive

Transmission from mother to child

Artificial

Artificial active

Vaccination (low dose of antigen introduced in the

body)

Artificial passive

Immunization (introduction of

antibodies in the body)

Classification of immunity

IMMUNITY

CELL MEDIATED

Activation of T lymphocytes,

PMN’s

Production of Tc, TH, Ts and memory T cells

Phagocytosis

HUMORAL

Production of B lymphocytes

Plasma cells

Produces Ableading to Ag-Ab reaction

Memory B cells

Helps in secondary

attack

Antibodies (Immunoglobulin)

Definition: An immunoglobulin, a specialized immune protein, produced because of the introduction of an antigen into the body, and which possesses the remarkable ability to combine with the very antigen that triggered its production.

Types of Immunoglobulins:IgG - protects the body fluidsIgA - protects the body surfacesIgM - protects the blood stream

IgD - serves as recognition receptors for antigensIgE - mediates allergic response or hypersensitivity

Need for vaccination

Dental caries is a major public health problem.

Has an impact on Oral health related quality of life

loss of man hours

Keyes triad

Newbrun tetrad

Fejerskov and Manji concept

(1990)

MICROBIOLOGY

A wide group of microorganisms are identified from carious lesions which include:

Mutans group of streptococci

S. mutans, S. sobrinus, S. crecitus, S. rattus, S. ferus, S. macacae, S. downei

Streptococcus mutans (initiation)

Lactobacillus (progression)

Actinomyces species (root surface)

Streptococcus mutans

PROFILE: Gram positive and facultative anaerobe

colonize the host only after the first teeth erupt, and their preferential colonization site is the teeth

they are highly localized on the surfaces of the teeth and their abundance in the plaque is highest over initial lesions

their level of colonization within the plaque is increased by sucrose consumption

they synthesize certain macro-molecules from sucrose that foster their attachment to the teeth

they are rapid producers of acid from simple carbohydrates (acidogenic), including sucrose, and are tolerant to low pH (aciduric).

they are essentially always recovered on cultivation of initial and established carious lesion sites

Antigenic determinants of S.

mutansADHESINS (WALL ASSOCIATED PROTEINS)

Form the 2 principal human pathogens of S.mutans (Ag I/II, Pac, or P1) and of S.sobrinus (Spa-A or Pag) and have been purified.

Ag I/II: Associated with binding or attachment of S. mutans with tooth surface

GLUCOSYLTRANSFERASE

S.mutans has 3 forms of GTF’s:

- Water insoluble glucan sythesizing enzyme: GTF-I

- Water insoluble & water-soluble glucan synthesizing enzymes: GTF-S-I.

- Water-soluble glucan synthesizing enzymes: GTF-S.

Genes encoding the 3 forms are:

- GTF-I: GTF-B - GTF-SI: GTF-C - GTF-S: GTF-D

Antigenic determinants

GLUCAN BINDING PROTEIN (GBP):

- S.mutans secretes at least 3 distinct proteins with glucan binding activity: GBP-A, GBP-B and GBP-C.

- It helps in binding of glucan to S. mutans

DEXTRANASES:

- Dextran is an important constituent of early dental plaque.

- Dextranase is an enzyme produced by mutans streptococus.

They destroy dextran and thus the bacteria can invade dextran-rich early plaque.

Dextran, when used as an antigen, can prevent the colonization of the organism in early dental plaque.

ROUTES OF

ADMINISTRATION

Common Mucosal Immune Pathway

Systemic Route

Active Gingivo-salivary Route

Routes of administration

COMMON MUCOSAL IMMUNE SYSTEM:

Mucosal applications of dental caries vaccines are generally preferred for the induction of Secretory-IgA antibodies.

Several routes which have been used for induction are as follows.

ORAL ROUTE:

Relied on oral induction of immunity in the GALT. Antigen was applied by oral feeding, gastric intubation, or in vaccine containing capsules or liposomes.

Routes of administration

INTRANASAL ROUTE:

Intranasal instillation of antigen, the NALT, has been used to induce immunity to bacterial antigens including those associated with mutans Streptococcus colonization and accumulation.

Routes of administration

TONSILLAR ROUTE:

The tonsillar tissues contain the required elements of immune induction of S-IgA and IgG.

Palatine tonsils, especially the nasopharyngeal tonsils have been suggested to contribute precursor cells to mucosal effector sites, such as salivary glands.

Routes of administration

MINOR SALIVARY GLAND

They populate the lips, cheeks and soft palate.

They have been suggested as potential routes for mucosal induction, given their short, broad secretory ducts that facilitate retrograde access of bacteria & their products & give the lymphatic tissue aggregates.

Routes of administration

RECTAL

This region as an inductive location for immune responses in humans is suggested as this site has the highest concentration of lymphoid follicles in the lower intestinal tract.

Hence the use of vaccine suppositories as an alternative in children in whom respiratory ailments preclude intranasal route may be considered.

Routes of administration

SYSTEMIC ROUTE

This route was used successfully and elicited predominantly IgG, IgM and IgA antibodies.

The antibodies find their way into the oral cavity via GCF and are protective against dental caries.

The development of serum IgG antibodies takes place within months of immunization. Protection against caries was associated predominantly with increased serum IgG antibodies.

Routes of administration

ACTIVE GINGIVO-SALIVARY ROUTE

In order to limit the potential side effects and to localize the immune response, gingival crevicular fluid has been used as the route of administration. It induces both IgA and IgG antibodies.

Routes of administration

PASSIVE IMMUNIZATION

It involves passive or external supplementation of the antibodies.

Several approaches tried were:

1. Monoclonal antibodies:

- Monoclonal antibodies to S.mutans cell surface Ag I/II have been investigated.

- Topical application in humans brought a marked reduction in the implanted S.mutans.

2. Bovine milk:

- Systemic immunization of cows with a vaccine using whole S.mutans

led to the products containing polyclonal IgG Abs.

- This milk was then added to the diet of a rat model which reduced caries

- This whey was also used in mouth rinse which resulted in lower

percentage of S.mutans in plaque.

3. Egg-yolk antibodies:

- Vaccines used were formalin killed whole cells & cell associated

GTFs.

- Caries reduction has been found with both these treatments.

4. Transgenic plants:

- Researches have developed a caries vaccine from a genetically

modified (GM) tobacco plant.

- Vaccine is colorless, tasteless and can be painted onto the teeth.

- It is the first plant derived vaccine from GM plants.

Passive immunization

Adjuvants and delivery systems of

caries vaccine

Synthetic Peptides

Coupling With Cholera Toxin Subunits

Fusing With Salmonella

Microcapsules And Macroparticles

Liposomes

ADVANTAGES

Prevents the disease in children

Can be incorporated to universal immunization programme

Cost effective in the long run

Provides life long immunity

DISADVANTAGES/PITFALLS

Clinical trials are few and concentrated only on S. mutans. As caries is multifactorial, it’s effectiveness is questionable

Risk of hypersensitivity

Cross reactivity of certain antigenic components of S. mutans with heart tissue (structurally similar to myosin)

Microbial resistance

PUBLIC HEALTH

PERSPECTIVE

Caries – declining trend due to various preventive measures

But are they effective enough ??

An effective, safe, and readily deliverable vaccine may not only help against pain and health issues associated with caries but also save the billions of dollars that are currently spent for restorative treatment.

Considerable caries reduction could be attained if colonization of S. mutans could be prevented or reduced at the time of eruption of both deciduous and permanent teeth.

Thus, a successful vaccination directed against S. mutans could be a valuable adjunct to other caries-preventive measures.

Public Health Perspective

SUMMARY

S.mutans is closely associated with dental caries.

Active and passive immunization strategies, which target key elements in the molecular pathogenesis of mutansstreptococci could be more helpful.

Integrating these approaches into broad-based public health programs may be of great value.

Analysis of the need, cost benefits, and risk-benefits of a vaccine against dental caries to be performed

For further reading refer . .

Hiremath S. S. Textbook of Preventive and Community Dentistry. (2nd edition). New Delhi: Elsevier; 2011

Shivakumar KM, Vidya SK, Chandu GN. Dental caries vaccine. Indian J Dent Res 2009;20:99-106.

Jason M. Tanzer et al. The Microbiology of Primary Dental Caries. J Dent Educ. 2001 Oct;65(10):1028-37

THANK YOU