1. DENTAL CARIES VACCINES

2. DENTAL CARIES VACCINES…. SUBMITTED BY Fathimathul Fairoosa.P

3. CONTENTS….. INTRODUCTION VACCINES APPROPRIATE IMMUNIZATION AGENTS
EXPERIMENTAL DESIGNS AIMED FOR SALIVARY IMMUNITY
EXPERIMENTAL DESIGNS AIMED FOR SYSTEMIC IMMUNITY
ROUTES OF VACCINATIONS
PROBLEM WITH CARIES VACCINES
PUBLIC HEALTH ASPECTS
CONCLUSION REFERENCE

4. DENTAL CARIES VACCINES……
INTRODUCTION
It is well known the fact that prevention of disease is hundred times better than cure.
Vaccination against tooth decay is an attempt to prevent dental decay.
The development of tooth decay requires,
a) Presence of cariogenic bacteria.
b) A sugar in the diet which is metabolized by the bacteria to form acid.
The process of caries development can be interfered by the presence of an effective immune response.

5. DENTAL CARIES …..

6. Vaccines……???
The word ‘vaccine’ derived from latin word which means a suspension of attenuated or killed micro organism (bacteria;virus) administrated for the prevention or treatment of infectious diseases.
It stimulate the production of protective antibody and other immune mechanism.
More recent preparations are sub unit vaccines and recombinant vaccines.

7. HOW IT WORKS…….????
The basis of a vaccine is that it keeps the patient in a state of readiness such that an infection does occur.
The immune response which is more rapid and effective can be mounted,thus during the first response both B and T lymphocytes form MEMORY CELLS that later remember the earlier attack and respond much better.

8. PRINCIPLES OF VACCINES…..
It must be safe for use in humans.
Contains appropriate virulent antigens mutans streptococci to induce antibodies.
Given via appropriate route to induce wanted response.
Cost effective.
Vaccine intended for non-lethal(caries) must be safer than vaccine for life threatening infection.

9. ANTIGEN….
An antigen has been defined as any substances which when introduced parenterally in to the body ,stimulates the production of an antibody with which it reacts specifically and in an observable manner.
ANTIBODY……
Antibodies are immunoglobulins present in the plasma.

10. TIME LINE……
Mucosal immunization of infants before the appearance of first teeth
study by CAUFIED et al- “Window of infectivity”
children become permanently colonized by mutans streptococci between middle of second year
& end of third year life
If children does not acquire mutans streptococci by 26 months of age then unlikely that primary teeth will be colonized

11. Factors affecting window of infectivity;
a)high maternal infection
b)high dietary sucrose level
children should immunize before window of infectivity

12. TIME LINES IN CHILDREN

13. HOST RESPONSE TO CARIES….
It can be mediated by secretory immune system (s-Ig A antibodies in saliva) or systemic immunity.
By 6-9 month,most children have adult like distribution of s-Ig A.

14. FACTORS AFFECTING WINDOW OF INFECTIVITY
a)high maternal infection
b)high dietary sucrose level
children should immunize before window of infectivity

15. A REVIEW…….
GOADBY was the first to advocate caries control by innoculation of the mouth with organism which would produce alkaline reaction.
The antigenic behaviour of LACTO BACILLUS ACIDOPHILUS was studied by CANBY in 1942.
GREEN in 1959,has found that caries resistance in a gp of dental students was associated with increased gamma globulins fraction in saliva.
BOWEN in 1969 showed that macaca irus immunized intra venously with s.mutans developed.
HAYASH et al in 1970 made an attempt on immunization with dextran sucrase and glycosidic hydrolase.
BOWEN in and COLE et al (1977) showed thatlactoferrine and lysozome posses anti bacterial effect invitro and therefore would exert considerable effect on bacterial flora invivo.

16. EXAMPLES OF VACCINES ARE….
A)Bacterial
eg: live- BCG for TB
killed-TAB for enteric fever
B)Viral
eg:live-oral poliyomyelitic vaccine
killed-salk vaccine for poliyomyelitis
C)Bacterial products
eg:toxoids for diphtheria

17. b)salivary leucocytes c)cell mediated immune response
Mainly the following three factors appear to play vital role in immunization against dental caries.
a)Micro organism
b)salivary leucocytes
c)cell mediated immune response

19. MICRO ORGANISM…
Much of the recent works on the bacteriology of dental caries suggest that the oral micro organism , particularly few strains of streptococci are important factors in the etiology of dental caries.
The mouth appears to be an ideal place for a wide variety of antibacterial substances in the saliva.
The activity of micro organism is greatly affected by the presence of these substances.

20. MICRO-ORGANISM

21. MICRO ORGANISM…
Much of the recent works on the bacteriology of dental caries suggest that the oral micro organism , particularly few strains of streptococci are important factors in the etiology of dental caries.
The mouth appears to be an ideal place for a wide variety of antibacterial substances in the saliva.
The activity of micro organism is greatly affected by the presence of these substances.

22. USES OF SPECIFIC ORGANISM..
1)STREPTO COCCUS MUTANS.
Facultative anaerobic organism producing extra cellular and intra cellular polysaccharides.
It is found in the plaque of carious teeth.
It cannot be isolated in the absence of dental caries.
It can be grown in pure culture.
Infection of germ free rats or normal hamsters with S.MUTANS has induce dental caries
The organism can then be recovered from the carious lesion and grown in pure culture.

23. CARIOGENECITY OF S.MUTANS HAS BEEN RELATED TO……..
Its unique combination of proteins.ie,ability to colonize on the teeth.
To produce extra and intra cellular polysaccharides.
To produce large amount of acids even at low pH value.
To utilize salivary glycoproteins.
Ability to synthesize an insoluble extra cellular
polysaccharide(dextran) from sucrose which
helps the organism to become attached to the teeth.

24. STREPTOCOCCUS MUTANS…

25. SALIVARY LEUCOCYTES…
All the available evidence indicate that there is close relationship between salivary leucocytes and freedom from caries.
Several studies are required to find out the techniques which increases the number of leucocytes and their phagocytic activity against dental cries.

26. CELL MEDIATED IMMUNE RESPONSE..
The increased DNA synthesis of lymphocytes from immunized monkeys stimulates with S.MUTANS is a T-cell dependent reaction.
B-cells are also capable of releasing lymphokines.
The immune response of S.MUTANS significantly correlated with IgG and IgA but not IgM antibodies.
The role of cell mediated immunity has been further explored by use of TRANSFER FACTOR.
This shows that protection against dental caries can be elicited by passive transfer of whole immune serum and cellular immunity.

27. LOCAL GINGIVAL IMMUNE RESPONSE
The possibility that the local gingival focus of plasma cell may contribute to the systemic antibodies passing in to the gingival domain has to be considered.
Although preliminary examination for antibody forming plasma cell to S.MUTANS in the gingiva has failed,this additional local source of antibodies cannot be excluded.

28. GLUCOSYL TRANSFERASES(GTF) WALL-ASSOCIATED PROTEINS. DEXTRANASE.
APPROPRIATE IMMUNIZATION AGENTS…
GLUCOSYL TRANSFERASES(GTF)
WALL-ASSOCIATED PROTEINS.
DEXTRANASE.
GLUCANS.
LIPOPTECHOIC ACID.

29. GLUCOSYL TRANSFERASE…
GTF are a group of extra cellular enzymes involved in the synthesis of polymers(glucan) from sucrose.
In rodent studies the use of GTF as an immunizing antigen has resulted concomitantly in an inhibition of S.MUTANS accumulation in dental plaque and caries reduction.

30. WALL ASSOCIATED PROTEINS…
Two purified proteins from the surface of S.MUTANS serotype C are currently being suggested for use as dental caries vaccines.
The other wall associated protiens is antigen A .

31. DEXTRANASE…
Large protein enzymes which break polymers of glucose into dextrans
These enzymes are probably used by oral streptococci to modify glucan products

32. These are tree like homo polymers of glucose
GLUCANS
These are tree like homo polymers of glucose
Two types of glucans:-
a)water soluble
b)water insoluble
They act as molecular and convection barriers, retain water and help in the adhesion of microorganism to the tooth surface.

33. Found in gram positive bacteria.
LIPOTEICHOIC ACID
Found in gram positive bacteria.
Exact role in dental caries pathogenesis is not clear

34. EXPERIMENTAL DESIGNS AIMED FOR SALIVARY IMMUNITY
These experiments were performed mostly in germ free rats
A) PERIGLANDULAR SALIVARY IMMUNISATION
B) IMMUNISATION BY COMBINED PERIGLANDULAR INJECTION AND INSTALLATION OF SREPTOCOCCUS MUTANS INTO THE PAROTID GLAND
C) ORAL SUBMUCOUS IMMUNISATION

35. PERIGLANDULAR SALIVARY IMMUNISATION
SUBCUTANEOUS INJECTION OF S.MUTANS (SALIVARY IgA ANTIBODY) RATS SALVARY GLAND REDUCED DENTAL CARIES

36. There was a reduction in the number of S.MUTANS on the teeth
SALIVARY GLAND IMMUNIZATION BY COMBINED PERIGLANDULAR INJECTION AND INSTALLATION OF S.MUTANS IN TO THE PAROTID.
Results in the formation of both salivary IgA and serum IgG and IgA antibodies.
There was a reduction in the number of S.MUTANS on the teeth
The serum antibody titres were much higher than those in saliva.
This regime also leas t some functional impairment of the salivary gland.

37. PARENTERAL IMMUNIZATION
Killed S.MUTANS were administrated to germ free rats in the drinking water for 45 days.
A significant reduction in caries was related to an increased level of salivary IgA antibodies.
IgA can be involved in the in the protection against cries has been involv

38. EXPERIMENTAL DESIGNS AIMED FOR SYSTEMIC IMMUNITY.
Mainly conducted in rats and rhesus monkey by using intra venous injection of live S.MUTANS.
The rhesus model monkey has been developed to induce caries and to immunize the monkey in a way that would be acceptable in man because of the following features.

39. IMMUNIZATION ROUTES…
LOCAL ROUTES
SYSTEMIC ROUTES

40. LOCAL ROUTES To avoid any systemic side effects
Established by passive immunization with IgG class of antibodies .
These antibodies find their way from circulation to gingival crevicular fluids through gingival epithelium to reach the tooth surfaces.

41. SYSTEMIC ROUTES…
Ingestion of S. MUTANS elicits predominantly a S- IgA response ,swallowing capsules containing S.MUTANS also increase in salivary IgA antibodies.
Subcutaneous immunization elicit serum antibodies
SYSTEMIC ACTIVE IMMUNIZATION.
Ingestion of a vaccine containing killed S.MUTANS daily for 10 consecutive days induced increased level of specific secretory IgA antibodies.
Resulted in reduction in number of viable S.MUTANS organism in dental plaque and whole saliva.

42. Systemic passive immunization
multivalent vaccine (s.mutans,serotype b,c,d,g). pregnant cow low plaque score (decreased no of streptococci in plaque) decreased caries activity

43. The sequence of cusp formation and calcification in the first permanent molars is comparable to that in man.
The pattern and rate of caries in the decidious dentition is consistant with that found in man.
The monkeys are fed entirely on a human type of diet.
The immune response also parallel those found in man.

44. ADVANTAGES OF VACCINATION
Prevent development of disease in children who show greatest incidence of dental caries
It can be given at the same time of vaccination against diphtheria and tetanus.
Immunity could be boosted thereafter at intervals to provide life long protection.
Existing delivery system of immunization can be used with out additional financial burden being increased.

45. LIMITATIONS IN DEVELOPMENT OF CARIES VACCINES.
The formation of a lesion involves destruction of tissue ,does not bring the organism into contact with the immune system & consequently there is no stimulation of immunoglobulin synthesis.
In dental caries some of the organism may combine by the immunogenic mechanism with the antibodies while others will share cross reacting antigens.
On vaccination , the net effect will be a reduction of the antibodies available for reaction with S. MUTANS.
An antibody may even promote back adherence by bonding to the tooth it will cause an increase in caries incidence.

46. ROLE OF PLANTS….
JULIAN .K.C.Ma reported that antibodies against dental caries can be produced in transgenic TOBACCO plant NICOTIANS TOBACCUM.
HYATT and co-workers (1989) showed that tobacco plant can be used to access component antibody from immunoglobulin chains. .

47. ADVANTAGES;
-Capacity of producing full length antibodies to complement mammalian protein assembly;which can be used to produce antibodies with altered properties.

48. ACTIVE IMMUNIZATION These includes :
- use of synthetic S.mutans peptides
- coupling S.mutans antigens to cholera toxin subunit
- fusing S.mutans genes with a virulent salmonella
- liposome delivery system

49. PASSIVE IMMUNIZATION Includes :
a) monoclonal antibodies topically applied b) immune bovine milk
c) egg yolk antibodies
d) transgenic plant antibody

50. FACTORS FOR A CARIES VACCINES: EFFICACY OF ORAL VACCINES.
FACTORS MITIGATING FOR AND AGAINST THE POSSIBILITY OF DENTAL CARIES VACCINES
FACTORS FOR A CARIES VACCINES:
EFFICACY OF ORAL VACCINES.
EFFICACY OF SYSTEMIC VACCINES.
NEED FOR A VACCINE IN A SELECTED POPULATIONS.
SAFETY OF ORAL VACCINES(NO SERUM ANTIBODIES)

51. FACTORS AGAINST A CARIES VACCINES…
LENGTH OF TIME FOR FDA APPROVAL.
FINANCIAL RESOURCES.
POSSIBLE LACK OF NEED IN POPULATION.

53. PUBLIC HEALTH ASPECTS..
An important questions always arises whether the research for caries vaccines is justified from a public aspect of views.
In addition it appears that by using a combination of water fluoridation and weekly fluoride mouth rinsing ,reduction of 70 to 80 percent can be achieved.
It is probable that caries vaccine could not be widely accepted by the general population.

54. CONCLUSION
Although conclusive evidence is not forth coming there is optimism that such a vaccine will eventually be developed and there for , vaccination against dental caries is not a dead issue.research towards development of caries vaccine seems to be justfied from the public health point of view and though it is a difficult problem the issue as such, is relevent and highly vital.

55. REFERENCE ESSENTIAL OF PREVENTIVE AND COMMUNITY DENTISTRY-SOBEN PETER
TEXT BOOK OF PEDIATRIC DENTISTRY-S.G DAMLE
TEXT BOOK OF PEDIATRIC DENTISTRY-SHOBHA TENDON
TEXT BOOK OF COMMUNITY DENTISTRY-SATHISH CHANDRA AND SHAHLEEN CHANDRA

56. THANK YOU