Periodontal vaccines: Where we are now and where we can go

INTRODUCTION

A chemical that is naturally dead or attenuated and delivered to the body with the goal of enhancing resistance to or curing a disease is referred to as a vaccine. The most well-known and significant application of immunological concepts to human health is vaccination. Vaccines are typically preventative, which means that they lessen the consequences of subsequent infections.^[1]

There are three types of vaccinations, which we will talk about in this review –

1. Active immunization – A method of stimulating a person’s immune system by giving them killed or live, attenuated products made of microorganisms.

2. Passive immunization – Immunization given passively, in which antibodies produced in one person are passed on to another.

3. DNA immunization – DNA vaccination involves giving a person DNA plasmids that include the genes needed to produce antigens.^[1]

Periodontitis is a disease of the periodontium (the tissue supporting the tooth structure). It is one of the most common diseases of the oral cavity. The etiological factors are both local as well as systemic, and hence, in addition to prompt tooth loss, it also affects a patient’s general health adversely.^[2]

According to the current model of periodontal disease, the host-microbial interactions have a major role in determining the degree and severity of tissue loss, even if periodontal pathogens are crucial for disease start. Periodontal diseases are immunological inflammatory reactions brought on by dental plaque microorganisms that, when harbored in a vulnerable periodontium, cause tissue deterioration, bone loss, and, ultimately, tooth loss.

The cowpox vaccine was the world’s first vaccine. Using the cross-protection offered by the cowpox virus, Edward Jenner devised and established the notion of vaccination in the late 18^th century. French microbiologist Louis Pasteur created the first anti-rabies vaccine in 1885. Even Pasteur did not fully comprehend immunological memory or the role of the lymphocyte; these topics had to wait another 50 years. The main mechanism was finally identified with Burnet’s clonal selections theory (1957) and the finding of T and B lymphocytes (1965).

It has been established that some chemicals signal periodontal tissue damage as the inflammatory response intensifies. They can be roughly categorized as (a) virulence factors for microorganisms and (b) those resulting from an inflammatory immune response in the host. Although bacteria are crucial because they initiate and maintain inflammation, host inflammatory mechanisms are responsible for the vast majority of tissue destruction. Lipopolysaccharides, bacterial enzymes, toxic compounds, microbial invasion techniques, fimbriae, bacterial deoxyribonucleic acid, and extracellular deoxyribonucleic acid are some examples of microbial virulence factors. The host-derived inflammatory mediators fall into three categories: Matrix metalloproteinases, prostaglandins, and cytokines.^[3]

Major periodontopathogens are Gram-negative anaerobic bacteria, which include Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, etc.

These bacteria create a wide range of antigens that excite cells that are pro-inflammatory and result in the release of several cytokines. Th1 or Th2 cells may be stimulated by certain antigens. Dendritic cells pick up antigens, which they then transmit to CD-8 or CD-4 cells along with major histocompatibility complex (MHC) antigens.

CD-8 cells → Response at Th 1 → Cell Mediated Immunity → Pro-inflammatory mediators

CD-4 cells → Response at Th 2 → Ab response → Protective mediators^[4]

Three periodontal vaccinations were used in the early 20^th century: Stock vaccines, autogenous vaccines, and pure cultures for Streptococcus and other pathogens. Examples include the Inava endocarp vaccine and the Vancott vaccination.

The need for vaccine development was brought on by bacteria that are capable of evading host immune responses and invading tissues, like P. gingivalis, which produces protease that not only provides peptides needed for its propagation but also breaks down serum-antibacterial components and immune cell-derived peptides, allowing it to hide from the components of the local gingival immune system by invading epithelial cells. Then, by penetrating endothelial cells, it might get out and into the bloodstream generally. To reduce the prevalence of systemic diseases linked to periodontal disease, patients must pay for periodontal therapy.^[5]

Periodontal disease does not yet have a preventative strategy, and available care is palliative. The availability of a periodontal vaccination would not only prevent or slow the progression of periodontal illnesses but also improve the standard of living for those who cannot easily access periodontal therapy.

MATERIAL AND METHODS

Since the topic has the potential to bring about a necessary change, a great amount of information could be found. Initially, Google Scholar was used to document a sample of the articles available for this review, after that databases such as Science Direct, ADA, FDI, and PubMed for articles published up to May 2023. We found nine peer-reviewed articles on the topic. The Internet, since it has a vast array of information, was used to gather the required insights into the topic. The sources on the Internet, written by professionals and published on reliable websites and journals, have been mentioned in the references.

TYPES OF PERIODONTAL VACCINATION

OTHER ROUTES OF VACCINE ADMINISTRATION

LIMITATIONS OF PERIODONTAL VACCINES

• Periodontal disease is complex and multifactorial

• Sustaining sufficient antibody levels over an extended time is a challenge

• Contamination of vaccines may be possible

• Toxic responses to fully inactivated vaccinations may occur.

FUTURE OF PERIODONTAL VACCINES

• Human trials of the conducted in vitro studies are a challenge currently

• A pan-gene approach is required to be undertaken, rather than focusing on only one at a time so that multiple representatives of the same gene can be included

• The future would be bright if research and development were focused toward the involvement of all pathogens rather than just one.

DISCUSSION

The multitude of pathogenic microorganisms suggests that the creation of a vaccination for periodontitis could be quite difficult, which is one of the main hurdles. The antigenic factors of bacteria may have an elevated likelihood of cross-reaction with human equivalents; hence, bacterial whole cells or a crude extract preparation for immunization is not preferred. Additional vaccines could contain undesirable proteins, poisons, or even live viruses, which would be dangerous for everyone but hypersensitive people. Attenuated vaccines may return to the wild kind;^[15] purportedly killed vaccines might not have been safely and properly destroyed. An immunocompromised recipient may have major worries about this. With the restriction of antigens displayed by antigen presentation cells, which hides immunomodulatory epitopes, animal models used for vaccine trials may reveal contradictions with human models in the MHC.

CONCLUSION

The present method of treating periodontitis is non-specific and focuses on the elimination of plaque using mechanical debridement, often requiring surgery. This continuous therapy is expensive, uncomfortable, and has a shaky prognosis because of low patient compliance.

The requirement for ongoing therapy to avoid the pathogen’s reestablishment restricts the usage of antibiotics. Vaccination may be a crucial supplementary therapy to mechanical debridement in people to prevent perio-pathogen colonization, but further study in this area may hold the key to the creation of periodontal vaccines. Against periodontitis and periodontitis-induced systemic illnesses, a complex vaccine design approach focusing on several pathogenic species is unquestionably required.