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Caries vaccine: a viable option?

By Maria Perno Goldie, RDH, MS

Vaccines are immuno-biological substances designed to produce specific protection against a given disease. They stimulate the production of a protective antibody and other immune mechanisms. Vaccines are prepared from live modified organisms, inactivated or killed organisms, extracted cellular fractions, toxoids, or a combination of these substances.(1)

Streptococcus mutans (S. mutans) has been identified as one of the major etiological agents of human dental caries. S. mutans posses various cell surface substances including adhesins, GTFs, and glucan binding proteins (GBP).(2) These substances are used for vaccine preparation. Most of the recent experimental efforts have been directed toward these compounds.

A caries vaccine is a vaccine to prevent and protect against tooth decay. A variety of different categories of vaccines are being developed at research centers. Development of a vaccine for dental caries has been studied for more than three decades. In 2003 The National Institute of Dental and Craniofacial Research (NIDCR) convened the Panel on Caries Vaccine.(3)

Discussion ensued about the issue of safety and how to evaluate it, the lack of colonization of S. mutans in a subset of the infant population, the burden of tooth decay and its effect on the quality of life, the lack of longitudinal studies that identify risk factors for colonization and outcomes, economic costs, and the role of the role of fluoride.

Some general issues in vaccine development were discussed. They included elements in successful vaccine development, the economic/risk benefit issue, industry partnerships, and models of care for access and delivery and an efficient delivery model for a vaccine.

The Panel made the following broad recommendations:
1. There is intrinsic value in learning more about the science in terms of the mucosal immune system and NIDCR should continue to support basic research in immunobiology.
2. Real world barriers have to be considered and surmounted if starting from the premise that a product will be delivered. It has been postulated that perhaps NIDCR should frame the goal for this project differently and provide guidance to the community. The approach can be to only reach to proof of principle in phase III trials.
3. There might be some intrinsic advantage to a passive immunity approach, both in terms of cost and of acceptance.
4. There is definitely a need for more longitudinal epidemiology correlates. This can be achieved through a “center’ where expert consultants can work with the core staff in addressing the various problems.
5. Advantage should be taken of natural experiments, especially children who are not colonized despite significant exposure. More research is needed on possible differences in innate (i.e., saliva) factors and on longitudinal follow-ups of how the oral environment changes.(3)

Generally, four routes of immunization have been used with S. mutans: oral; systemic (subcutaneous); active gingivo-salivary; and passive dental immunization.(4) As the name suggests, passive immunization involves passive or external supplementation of the antibodies. As mentioned previously, some intrinsic advantage to a passive immunity approach, both in terms of cost and of acceptance. However, there is the disadvantage of repeated applications, as the immunity conferred is temporary.

One approach tried was monoclonal antibodies. The latest in these developments in passive immunization is the use of transgenic plants to give the antibodies. The researchers have developed a caries vaccine from a genetically modified (GM) tobacco plant.(5) The vaccine, which is colorless and tasteless, can be painted onto the teeth rather than injected and is the first plant derived vaccine from GM plants.

Active and passive immunization strategies, which target key elements in the molecular pathogenesis of mutans Streptococci, hold promise to controlling this disease process. Integrating these approaches into broad-based public health programs may prevent dental caries disease in many of the world's children, among whom those of high risk might derive the greatest benefit.

In conjunction with established methods of caries prevention, caries vaccines have the potential of making a highly valuable contribution to disease control. Meanwhile, basic research on the mode of action of caries vaccine and the search for new, more effective, and possibly polyvalent vaccines (vaccines that can vaccinate a person against more than one strain of a disease) must continue if we are to fully explore their potential to minimize dental caries.

Regardless of the mechanism by which immune protection against dental caries is achieved, further advances to make immunization against caries practical will depend upon clinical trials aimed at establishing whether the findings from animal experiments can be transferred to humans. Particular goals for such studies include determining whether appropriate immune responses can be safely generated in humans, especially in susceptible age groups, and whether such responses will afford desirable levels of protection.

The goals for vaccination against most other, mainly acute, infectious diseases are usually to provide near-complete protection of the individual against infection, and to achieve a sufficiently prevalence of immunity in a population that the chain of transmission is broken and the pathogen cannot sustain itself in the community.(6) However, the biology of caries is different from that of acute infections, and as with other modalities of intervention.

it is conceivable that immunization will not attain complete effectiveness. However efficacy as low as 50% could have significant impact on the burden of this disease, and the social and economic costs associated with it. As the bulk of dental caries have been shown to occur among a high risk segment of the population in the USA, targeting an effective vaccine to such individuals would increase its impact.

On March 20, 2010, the NIDCR updated its recommendations with a Summary of Vaccine Panel's Deliberations and Recommendations. They concluded that NIDCR should continue to support basic research on mucosal immunology and suggested that priority be given to the passive immunization approach. The panel also raised several scientific, ethical and economic considerations related to the active immunization approach for the prevention of dental caries.(7)

They questioned whether organisms other than S. mutans cause caries, since current vaccine strategies have targeted this organism. The possibility of other pathogenic organisms moving into the niche vacated by S. mutans was considered. Concern was articulated about the safety of some of the antigens being proposed by the caries vaccine research groups. The panel raised the question of whether immunization of children, ages 1-2 years, whose immune systems are still developing, would present unique safety issues relative to older children or adults.(7) It was emphasized that specific identification of the target population for a caries vaccine and the rationale be outlined.

Questions about the possibility of a vaccine ever coming to market were expressed due to public perception about the “risks” of vaccines. The biggest obstacle would be getting a CDC Advisory Committee on Immunization Practices (ACIP: www.cdc.gov/vaccines/recs/acip/default.htm) recommendation for routine use in all children. If that is not obtained, it is feared that industry will not manufacture the vaccine. An ACIP recommendation is based on economic-risk benefit, making it necessary to prove that a caries vaccine would be cost saving and cost effective.

It was shown in an animal study that a mixture of S. mutans surface proteins, enriched with fimbria components, appears to be a promising immunogen candidate for a mucosal vaccine against dental caries.(7) More information about the burden of caries over time in terms of both economics and quality of life will be required.(8) Is a caries vaccine a viable option in dental caries and decay prevention? You be the judge!

References
1. Park K. Text book of preventive and social medicine. 17th ed. Bhanotidas Publication; 2004.
2. Koga T, Oho T, Shimazaki Y , Nakano Y. Immunization against dental caries. Vaccine 2002;20:2027-44.
3. "Panel on Caries Vaccine". National Institute of Dental and Craniofacial Research of the National Institute of Health. January 28, 2003. www.nidcr.nih.gov/Research/ResearchPriorities/ExpertPanelsOnScientificOpportunities/PanelOnCariesVacine.htm Accessed January 21, 2011
4. Shivakumar KM, Vidya SK, Chandu GN. Dental caries vaccine. Indian J Dent Res 2009;20:99-106
5. News. Genes 'n' Greens: The future of oral medicine? Br Dent J 2002;192:674.
6. Russell MW, Childers NK, Michalek SM, Smith DJ, and Martin A. Taubmand. A Caries Vaccine? The State of the Science of Immunization against Dental Caries. Caries Res 2004;38:230-235.
7. Fontana M, Dunipace AJ, Stookey GK, and Gregory RL. Intranasal Immunization against Dental Caries with a Streptococcus mutans-Enriched Fimbrial Preparation. Clinical And Diagnostic Laboratory Immunology, May 1999, P. 405–409.
8. www.nidcr.nih.gov/Research/ResearchPriorities/ExpertPanelsOnScientificOpportunities/SummaryOfVaccinePanels.htm

Additional Reading
1. CaroRx--Planet produced the world's first clinically tested Plantibody, CaroRx. CaroRx binds specifically to Streptococcus mutans, the bacteria that cause tooth decay, and prevents the bacteria from adhering to teeth. CaroRx is intended for regular topical preventative administration by both dental hygienists and patients following a thorough cleaning and intervention for any existing decay. www.planetbiotechnology.com/products.html#carorx
2. www.facebook.com/pages/Caries-vaccine/140157416003702
3. A Caries Vaccine? content.karger.com/ProdukteDB/produkte.asp
4. Caries Vaccines for the Twenty-First Century www.jdentaled.org/cgi/reprint/67/10/1130.pdf
5. Thesis-Passive Immunization Against Oral Pathogens diss.kib.ki.se/2004/91-7349-960-9/thesis.pdf
6. The Science and Practice of Caries Prevention
www.happyteeth.org/media/pdf/Featherstone2000SciPracticeCariesPrevention.pdf 


Maria Perno Goldie, RDH, MS

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