CARIES VACCINE….
Most common/widespread-Infectious disease
of mankind.
Once acquired-persists throughout life,even if
treated.
Potentially transmissible.
IS CARIES CONQUERED???..
“WINDOW OF INFECTIVITY”{Caufield et
al,1993}
Source of infection- Maternal.
Environmental conditions.
Children who do not become infected by 3yrs.
appear to remain uninfected for several
yrs.,possibly until eruption of the secondary
dentition.{Caufield et al,1993:Smith et al,1998}
Hence, immunization could be used to protect
the child against caries in this critical period.
Underwood & Milles(1881)-Bacteria are
involved in pathogenesis of dental caries.
Miller(1890)-chemicoparasitic theory of
dental caries.
J.K.Clarke(1924)-specific microorganism
[Streptococcus mutans] is associated
with dental caries.
Since dental caries fulfills the criteria for
infectious disease, possibilities of
vaccination have been considered.
VACCINE:
Immunobiological substance designed to
produce specific protection against given
disease. It is a suspension of attenuated or
killed microorganisms, administered for the
prevention or treatment of infectious
diseases.
They may be prepared from live modified
organisms, inactivated or killed organisms,
cellular fractions, toxoids or combinations of
these.
Antigen – any substance which stimulates
production of antibody with which it reacts
specifically and in an observable manner.
Antibody – substance which appears in
serum/tissue fluids which react with the
antigen specifically and in an observable
manner.
Immunity- host resistance towards injury
caused by microbes or products.
Natural host immunity (IgA):-
Secretory immunity against mutans.
2nd.most abundant Ig- generated by “common
mucosal immune system.”
10% of serum Ig= 0.6-4.2mg./ml.
Half life=6-8 days.
2 types---Secretory IgA
Serum IgA
-Secretory IgA-115dimer.
-2 IgAs joined by J-chain+one secretory/transport
piece.
-Saliva= 100-300 g/ml.
-Local immunity, Resistant to digestive enzymes.
Functions of IgA:-
Inhibits adherence of micro-organisms,
colonization.
Promotes phagocytosis/extracellular killing of
micro-organisms.
Neutralizes microbial enzymes/toxins.
Activates alternate complement pathway.
Specifically eliminates Mutans-phagocytosis
/swallowing.
2 types---IgA1—60%
IgA2
Mestecky & Russell1986
Inducing IgA immunizations through new
strategies of mucosal immunization—Induce
Secretory IgA Ab without complication of
parenteral immunization.
MOLECULAR PATHOGENESIS OF CARIES
Glucans accumulation of S.
+ mutans in biofilm
(GTFs + GBPs)
NEXT PHASE OF
PATHOGENESIS
Accumulated Strep.mutans most
prolifically produce lactic acid.(Gibbons
&Van Houte, 1975)
If this increase in lactic acid synthesis
can’t be sufficiently buffered, Dental
caries ensues.
Effective molecular targets for dental
caries vaccines
response.
LIPOSOMES
Phospolipid membrane vesicles are used to
contain and deliver drugs and antigens.
Improve mucosal immune responses by
felicitating M cell uptake and delivery of
antigen to lymphoid elements of inductive
tissue .
IgA1 antibody response was higher with
liposome containing compared to protein
vaccine alone.
ACTIVE IMMUZATION
Immunization with GTFs from S.mutans or
S.sobrinus leads to formation of salivary IgA
antibodies
Oral immunization using enteric–coated
capsules filled with crude mutans GTF antigen
preparations which are contained in
liposomes.
Nasal immunization with dehydrated
liposomes containing GTF preparation induces
IgA1 antibody response.
topical administration of GTF on lower
lip caused a delay in S.mutans
reemergence.
Mucosal immunization with dental caries
vaccines could be protective, especially
in pediatric population where S mutans
is not yet a permanent member of the
bio-film.
Passive immunization
Mouth rinses containing bovine milk or hen egg
yolk IgY antibody to S mutans cells led to
decrease in S mutans in saliva and dental plaque.
Topical application of mouse monoclonal IgG or
transgenic plant secretory SIgA/G antibody, each
with specificity for Ag I/II.
Following antibacterial treatment, antibody was
topically applied for 3 weeks.Recolonization with
S mutans did not occur for atleast 2 years after
treatment with mouse monoclonal antibody.
PROSPECTS AND CONCERNS
For populations under normal risk of
infections Immunization for dental caries
should begin early in the second year of life.
If bacterial colonization of the dental bio-film
is complete after eruption of all primary teeth
and if through immunization we can prevent
S mutans colonization prior to this period
then benefit of early immunization extends
until secondary teeth begin to erupt.
“What is the ideal dental
caries vaccine approach”
A vaccine giving broadest coverage.
To intercept infection by all common S-
mutans strains.
For both low and high risk populations.
Whose immunity would last through primary
and secondary infection periods.
Given with other immunizations.
Given by various routes and still be effective.
Inexpensive.
Delivered by individuals with little
training.
Can or should we expect all of these
characteristics in one vaccine?????......
E.g., ideal vaccination application for a
child with asthma may be at a site e.g.,
rectal and with an adjuvant e.g.,
detoxified CT.
Dental caries vaccine would be the first
non living vaccine to be applied by any
mucosal route during the first three
years of life.
High risk populations may require both
active and passive mechanism for
protection.
Understanding the signals for colonization
and growth of cariogenic streptococci in
dental bio-films may help us devise more
informed and refined techniques to “
LOCK OUT ” those bacteria that can cause
us harm.
Why is caries vaccine a dead
issue ???????
Unlike small pox or measles, S. mutans
is only partial responsible for dental
caries.
Dental caries develops on a non living
and non shedding body surface.
( isolated from the activity of
phagocytic cells and complement )
REFERENCES
CARIOLOGY TODAY. 1983,285 – 292.
CRIT.REV.ORAL BIO MED. 13(4), 335 -
49,2002.
J. DENT EDU VOL 67,NO. 10,2003.
CARIES RES,2004,38: 230-35.
OPER.DENT. 6,2001, 51-60.
J DENT. RES. 83(3): 266-70, 2004.
CARIES RES. 1999: 4-15.
J. DENT. RES. 75(8), 1996.
Thank you...