Is A Mucosal Vaccine for Dysbiotic Periodontal Disease on the Horizon?
Periodontal disease is quite possibly the most common chronic inflammatory disease found in humans. Scientific evidence has well established its role in some systemic diseases. Research has led to the conclusion that periodontal disease is multifaceted, with the microbiome and certain bacterium being one of the causative factors. The complex polymicrobial biofilm is where we look to determine the etiology in many cases.
The red complex bacteria are indicated in severe cases of periodontal disease. The red complex is composed of Bacteroides T. forsythus, P. gingivalis, and T. denticola. Though the host response plays a role in the onset and progression of periodontal disease, these bacteria are also an important factor. I mention this because in many cases the presence of these bacteria alone will not lead to periodontal disease.
Currently, periodontal disease is considered a chronic disease, there is no cure. Prevention and maintenance are our best tools in combating periodontal disease. Prevention currently consists of patients visiting the dentist/dental hygienist regularly and being compliant with home care. As a practicing clinician, I can assure you patient compliance is low. Though my experience is anecdotal, my statement is supported by the CDC’s estimate of 47.2% of adults over age 30 that have some form of periodontal disease. 
How do we fight a disease that has plagued humans for centuries and is quite common amongst us? A group of scientists are working on a possible answer, in a study published March 2019 in Mucosal Immunology, scientists share their findings in a search for a built-in adjuvant-engineered mucosal vaccine against dysbiotic periodontal diseases.
The authors acknowledge a monovalent vaccine would not be ideal in the prevention of periodontal disease, as periodontal disease involves multiple bacteria in the onset and progression. Therefore, the authors worked on a divalent vaccine that would address multiple pathogenic bacteria in hopes to reduce the possibility of a dysbiotic state of the microbiome.
The target of the divalent vaccine includes the Hgp44 domain polypeptide of RgpA of P. gingivalis, and the envelope protein FomA found on the outer membrane of F. nucleatum. If successful, this would suppress one bacterium in the red complex and one in the orange complex in hopes of keeping the microbiome in homeostasis.
Though F. nucleatum is a member of the orange complex, inhibiting its ability to bridge between early and late colonizing bacteria would eliminate the need for vaccines that target Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Eubacterium spp., Tannerella forsythia, Selenomonas flueggei, and Treponema denticola. If these bacteria are unable to have cell to cell interaction due to the absence of F. nucleatum, ideally this would render them useless in the pathogenesis of periodontal disease. Moreover, F. nucleatum is associated with a wide spectrum of systemic diseases, including GI disorders, cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre’s syndrome, and Alzheimer’s disease.
The vaccine may be beneficial for additional systemic diseases by inhibiting the Hgp44 domain polypeptide domain of RgpA of P. gingivalis which is associated with platelet aggregation and atherosclerotic inflammation.
Ideally, the vaccine will elicit both a systemic immune response as well as a mucosal immune response. The adjuvant used in creating this vaccine is bacterial flagellin, Vibrio vulnificus FlaB. Vibrio vulnificus FlaB has been shown in previous studies to have a strong mucosal adjuvant activity that induces protective immunity.
The formula for the vaccine is tFomA-FlaB and Hgp44-FlaB. The intranasal vaccine showed antibody responses in serum and salivary secretions. Interestingly, the antiserum used to check efficacy appeared to recognize a 30 kDa band in P. endodontalis. This suggests the divalent vaccine should be active against diverse Fusobacteria. Additionally, immunoglobulins from the divalent vaccine inhibit co-aggregation between P. gingivalis and T. denticola.
This study shows that the divalent vaccine provides optimal protective immune responses to P. gingivalis and F. nucleatum inhibiting alveolar bone loss. The vaccine not only interacts with bacteria aggregation and biofilm formation but also with host-bacteria interactions on the mucosal surface.
Though I would welcome a vaccine that could prevent periodontal disease and possibly some systemic diseases associated with periodontal disease, this vaccine is in the exceedingly early stages of development. This study was an animal model, meaning this may take 10-20 years to develop if at all. Vaccine science is complicated, and most vaccines never make it to market. As a matter of fact, only 6% of vaccines make it through trials and are marketed to the public.
I remain cautiously optimistic about this vaccine and I look forward to following it through the many clinical trials required to be marketed to the public. If you are a dental professional and this vaccine was to make it through trials would you be willing to recommend and administer this vaccine to patients? If you are a patient that could benefit from this vaccine would you be willing to have it administered? I can say with great confidence I would certainly add it to my armamentarium of tools to keep my patients healthy in the event it makes it through trials and is available to the public.
1. Centers for Disease Control and Prevention. Periodontal Disease. Retrieved from https://www.cdc.gov/oralhealth/conditions/periodontal-disease.html
2. Puth S, Hong SH, Na HS, et al. A built-in adjuvant-engineered mucosal vaccine against dysbiotic periodontal diseases. Mucosal Immunol. 2019;12(2):565-579. doi:10.1038/s41385-018-0104-6. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30487648/
3. Lee SE, Kim SY, Jeong BC, et al. A bacterial flagellin, Vibrio vulnificus FlaB, has a strong mucosal adjuvant activity to induce protective immunity. Infect Immun. 2006;74(1):694-702. doi:10.1128/IAI.74.1.694-702.2006. Retrieved from https://pubmed.ncbi.nlm.nih.gov/16369026/