Running head: DENTAL CARIES VACCINES
Vaccines Against Dental Caries
Ivette Hernandez
Gabriela Jones
Miami Dade College
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DENTAL CARIES VACCINES
Vaccines Against Dental Caries
Introduction
Dental caries is an infectious, transmissible, communicable disease that has reached
epidemic proportions affecting unevenly distributed population of all ages all over the world
(Gambhir, et al., 2012; Wilkins, 2013). According to the Surgeon General (2003), tooth decay is
the most prevalent chronic childhood disease in the United States, not to mention that 91% of
dentate adults have had at least one dental caries experience (Gambhir, et al., 2012).
Conventional caries preventive strategies such as oral health education, diet modification,
application of fluoride and sealant placements have not been effective enough to overcome
behavioral, economic, and/or cultural barriers that still render the disease pandemic (Gambhir, et
al., 2012). Studies have been conducted for more than seven decades to find an innovative
approach to proficiently fight caries through the development of a vaccine (Smith & Spatafora,
2012; Smith, 2012).
This research paper will give a glimpse into different approaches in the development of
vaccines against dental cavities.
Background
The first trials of dental caries vaccines containing lactobacilli were introduced in the
1940s, which, due to limited pathogenesis information and uncertain virulence characteristics,
deemed ineffective (Smith, 2003). It was not until the 1960s that breakthrough experiments
proved that Streptococcus mutans were the primary causative agents in dental caries
development (Smith, 2002). It was revealed that once this microorganism was settled in the oral
environment it was arduous to combat; therefore, great importance has been given to the
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modification of the early stages of colonization. Studies show that the critical period of S. mutans
establishment occurs in children between two to three years of age, referred to as the “window of
infectivity” (Smith, 2002). According to D. J. Smith (2003), “the ‘window’ may open even
earlier if maternal S. mutans infection levels are high, coupled with frequent exposure to dietary
sucrose” (p. 1131). Hence, findings advise that the “window of vaccine opportunity” would be
between twelve and eighteen months of age (Smith, 2002).
Discussion
The onset to dental cavities begins with the acidification of plaque by the accumulation of
lactic acid on the tooth surface. Lactic acid is produced as cariogenic bacteria metabolize
fermentable carbohydrates present in the oral environment, usually after sucrose ingestion
(Gambhir, et al., 2012; Smith & Spatafora, 2012; Wilkins, 2013). The main microorganisms that
are usually involved in the pathogenic process would include Streptococcus mutans, S. sobrinus,
Lactobacillus acidophilus, L. fermentum, and Actinomyces viscosus (Gambhir, et al., 2012;
Smith & Spatafora, 2012). Of all, S. mutans plays the most significant role in caries
development.
“The molecular pathogenesis of mutans streptococci involves several phases, each of
which offers targets for immunological intervention” (Smith, 2003, p. 1132). However, best
results would be attained when S. mutants are restrained from lodging onto the tooth surface
within the “window of vaccine opportunity” period. Antibody-mediated aggregation has been
proven to be effective in clearing microorganisms from the oral cavity during the salivary phase
by blocking necessary receptors for colonization or aggregation. Adhesins, glucan-binding
domains of glucan-binding proteins (GBP), and disabling glucosyltransferases (GTF) enzymes
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that are responsible for glucan production are the main target. Other aims include the alteration
of metabolic processes and the enhancement of salivary IgA antibody function (Smith, 2003).
IgA is the principal antibody secreted by salivary glands. With the induction of this
immunoglobulin in the oral mucosa, studies have shown that other organs and parts of the body
lined by mucosal tissue, such as nasal and rectal sites, present an induced immune response
against the specific antigen. For this reason, mucosal applications of a dental vaccine are the
favored method and have created the “common mucosal immune system” and now, numerous
mucosal paths have been used to encourage the immune response necessary against dental caries
antigens (Smith, 2003).
The oral route has been used to induce immunity in gut-associated lymphoid tissue
(GALT). “In these studies, an antigen was applied by oral feeding, gastric intubation, or in
vaccine-containing capsules or liposomes” (Chandu, Shivakumar, & Vidya, 2009, p. 99). The
antigen denaturing properties of stomach acids and distant inductive sites rendered the oral route
less than ideal (Smith, 2003). On the other hand, nasal-associated lymphoid tissue (NALT) is
targeted via intranasal route eliciting much higher IgA immune response. Since this route of
immunization doesn’t expose the antigens to low pH and other several destructive enzymes,
lesser doses of antigens are required, making this route more suitable and satisfactory than other
mucosal distribution methods (Xu, et al., 2006). An alternative for children with some type of
respiratory impairment that would disable them from receiving the vaccine intranasally would be
the intrarectal mode of application. “The colo-rectal region as an inductive location for mucosal
immune responses in humans is suggested from the fact that this site has the highest
concentration of lymphoid follicles in the lower intestinal tract” (Smith, 2002, p. 343). Moreover,
palatine tonsils and nasopharyngeal tonsils are of especial consideration for the tonsillar route
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due to their contribution of precursor cells to salivary glands, often referred as mucosal effectors
sites. Even though the tonsillar tissue possesses the necessary elements for immune response, it
involves an IgG response rather than IgA. Nevertheless, recurrent tonsillar topical administration
of formalin-killed S. sobrinus has been shown to promote the appearance of IgA antibodyproducing cells in both, major and minor salivary glands (Smith, 2003).
Particular studies have reported that the systemic route approach attained positive results
against dental caries. IgA, IgM and IgG antibodies were effectively formed after subcutaneous
injection of S.mutans, which later found their way into the oral cavity via the gingival crevicular
fluid. IgM antibodies were the least likely to thrive; IgA showed a slow increase whereas high
titer of IgG antibodies persevered. It is imperative to note, however, that the IgG antibody
development will take months after vaccination (Gambhir, et al., 2012).
Passive immunization is another method considered to battle tooth decay. With this
particular tactic, “there is no induction of immunological memory, and the administered
antibodies can persist in the mouth for only a few hours at most or up to three days in plaque”
(Gambhir, et al., 2012, p. 4). This could be attained by the use of mouth rinses with IgY
antibody, resulting in a short-range diminution of S. mutans in dental plaque. The most up-todate development regarding passive immunity would involve the use of transgenic plant,
Nicotiana tabacum. This vaccine would characteristically be tasteless and instead of being
injected, would be topically applied to the teeth. This would be the first plant derived vaccine.
Likewise, ongoing research at the London Guys Hospital is aiming to sequester a specific
peptide that prevents the bacterium S. mutans from adhering to tooth surfaces. The targeted
delivery route is by mouth, through apples and strawberries (Gambhir, et al., 2012).
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History shows successful results of DNA vaccination against dental cavities causative
agents. “A DNA vaccine is a bacterial plasmid that is designed to express a gene for the antigen
of interest in the cells of a host” (Xu, et al., 2006, p. 916). A new fusion DNA vaccine is being
researched at Wuhan Institute of Virology, China, based on two important virulence factors of
the bacterium S.mutans, the cell surface protein PAc and glucotransferases GTFs. This
experiment presents positive outcomes with gnotobiotic animals; the fusion vaccine could give
rise to rapid and improved immunoglobulin activity in serum and saliva in contrast to non-fusion
DNA vaccine. Conversely, this fusion DNA vaccine had a weak response against S.sobrinus
microorganism (Gambhir, et al., 2012).
Conclusion
Despite numerous scientific advances to combat intraoral diseases, dental cavities remain
a widespread issue for oral health. This, however, can’t lead to the misconception that the disease
is not serious or relevant. Every new detail from researches can bring fresh clues on how to
prevent this illness from happening; the development of a vaccine seems to be the most
promising and exciting project in progress to accomplish that. For the near future, it is expected
that at least one of the several routes and methods being currently studied will provide definitive
results and will be put into practice. This will tremendously help the population all over the
world, especially children with less access to education and preventive methods against dental
caries.
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References
Chandu, G., Shivakumar, K., & Vidya, S. (2009). Dental caries vaccine. Indian Journal of
Dental Research, 20(1), 99-106. Retrieved from
http://go.galegroup.com.db16.linccweb.org/ps/i.do?id=GALE%7CA197226657&v=2.1&
u=lincclin_mdcc&it=r&p=AONE&sw=w
Gambhir, R. S., Singh, S., Singh, G., Singh, R., Nanda, T., & Kakar, H. (2012, April). Vaccine
against dental caries-an urgent need. Vaccines & Vaccination, 3(2), 1-7.
doi:10.4172/2157-7560.1000136
Smith, D. J. (2002, July). Dental caries vaccines: Prospects and concerns. Critical Reviews in
Oral Biology & Medicine, 13, 335-349. doi:10.1177/154411130201300404
Smith, D. J. (2003, October ). Caries vaccines for the twenty-first century. Journal of Dental
Education, 67(10), 1130-1139. Retrieved from
http://www.jdentaled.org/content/67/10/1130.full.pdf
Smith, D. J. (2012, March). Prospects in caries vaccine development. Journal of Dental
Research, 91(3), 225-226. doi:10.1177/0022034511425928
Smith, E. G., & Spatafora, G. A. (2012, February). Gene regulation in S. mutans : Complex
control in a complex cnvironment. Journal of Dental Research, 91(2), 133-141.
doi:10.1177/0022034511415415
U.S. Department of Health and Human Services. (2003). National call to action to promote oral
health. Retrieved from
http://www.surgeongeneral.gov/library/calls/oralhealth/nationalcalltoaction.pdf
Wilkins, E. (2013). Clinical Practice of the Dental Hygienist (11th ed.). Philadelphia, PA:
Lippincott Williams & Wilkins.
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Xu, Q. A., Yu, F., Fan, M. W., Bian, Z., Chen, Z., Fan, B., Guo, J. H. (2006, October).
Immunogenicity and persistence of a targeted anti-caries DNA vaccine. Journal of Dental
Research, 85(10), 915-918. doi:10.1177/154405910608501008