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Oral route:
The oral route of administration has concentrated on stimulation of the secretory IgA antibodies via
the common mucosal system (consisting of MALT and GALT), which is activated in the special cells of the
intestinal tract.

For the colonization of Streptococcus mutans in oral cavity, the enzyme Glucosyltransferase is of
paramount importance. Thus, several studies have been carried out using it.

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The disadvantages associated with the oral route of delivery is the proteins and peptides rapid
break down. But, it is also considered safer than the systemic route due to the concern of cross reactivity to
the Streptococcal antigens.
Systemic route:
The subcutaneous administration of Streptococcus mutans has been tried out in monkeys and it
elicited predominantly IgG, IgA and IgM antibodies. These were found to enter the oral cavity through the
gingival crevicular fluid.
Active gingivo-salivary route:

The use of caries vaccine with other routes has been some concern expressed particularly regarding their side
effects. Thus, to limit all these potential side effects and also to localize the immune response, GCF has been
used as a route of administration. It is also associated with the increased levels of IgA apart from IgG.
The various modalities tried out were:
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Direct injection of lyzozyme into the rabbit gingival which has elicited local antibody forming cell
response.
Brushing live Streptococcus mutans onto the rhesus monkeys gingiva (which failed to activate
antibody formation).

Use of smaller molecular weight of Streptococci antigen has resulted in better performance. This is
probably due to the better penetration.
Active immunization:

Various new approach have been tried out in order to overcome the existing disadvantages.
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Synthetic peptides:
Any antigen derived from animals or humans has the potential for hypersensitivity reaction. The chemically
synthesized peptides hold on advantage in that this reactivity can be avoided. This has also been found
enhance the immune response. In humans, synthetic peptides elicited both IgG and T-cell proliferative
response, and the antibodies were both anti-peptide and anti-native.

The synthetic peptides give antibodies both in the gingival crevicular fluid and in the saliva. This synthetic
peptide is the Glucosyltransferase enzyme derivative.
Coupling with cholera toxin subunits:
It has been found that coupling of the protein with nontoxic unit of the cholera toxin was effective in
suppressing the colonization of Streptococcus mutans. This approach was tried out as the cholera toxin
binds effectively to the lymphoid cells and functions as an excellent adjuvant. The intraoral route of
administration was tried out by Katz in 1993.
Fusing with Salmonella:
The avirulent strains of Salmonella is an effective vaccine vector so that fusion using recombinant
techniques have been used.
Liposomes:
These have used in the delivery of several, particularly anticancer drugs so as to effectively attack the cells
on the targeted site. These liposomes are closed vesicles with bi-layered phospholipid membrane. The
efficacy using liposomes has been found to increase two fold in a rat model. In humans, increased IgA
antibodies have been found.

Passive immunization:
As its name suggests, this immunization involves external or passive supplementation of antibodies. This has a
disadvantage of repeated applications as its immunity conferred is temporary. There are several approaches
which are tried out and are mentioned below:
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Monoclonal antibodies:
They have investigated these Monoclonal antibodies to the cell surface antigen I or II of Streptococcus
mutans. These topical applications in the human subjects have showed a marked reduction in this
implanted Streptococcus mutans. Thus, by bypassing this system very less concern exists regarding the
potential side effects of

caries vaccine
.
Bovine milk and whey:

A systemic immunization of the cows with the vaccine using the whole Streptococcius mutans lead to the
bovine whey and milk containing IgG antibodies. This was later added to a rat models diet. The immune
whey showed a reduction in the caries level.
This whey was used in the mouth rinses by Filler et al (1991). This resulted in lower percentage of
Streptococcus mutans of plaque.
Egg-yolk antibodies:

Hamada (1990) introduced this concept of using antibodies of hen egg-yolk against the cell associated with
glucosyltransferase of Streptococcus mutans. Vaccines used were cell associated glucosyltransferase and
formalin-killed whole cells. Caries reduction has also been seen with both these cell treatments.
Transgenic plants:
Latest in these developments in the passive immunization is the usage of transgenic plants for the
antibodies. They have the following advantages:

The genetic part can be exchanged easily.

It is also possible to manipulate the structure of the antibody such that the antibody
specificity is maintained, but the constant region of the antibody can be modified in order to adapt to
the human conditions. This helps in avoiding cross reactivity.

A Large scale production is also possible as it would be quite cheap.