Year : 2016 | Volume
: 2 | Issue : 1 | Page : 10--13
Periodontal vaccine: A new vista in periodontology - A review
Chandni Gupta, D Deepa
Department of Periodontology, Subharti Dental College and Hospital, Meerut, Uttar Pradesh, India
Department of Periodontology, Subharti Dental College and Hospital, Meerut - 250 005, Uttar Pradesh
The infectious etiology of periodontitis is complex. Due to its high prevalence rate, this disease has created an interest in finding a solution in the form of vaccines. Vaccination is the best known and the most important application of immunological principles to human health. The complexity of the periodontopathic bacteria might be a problem in the determination of antigens, thus complicating the development of periodontal vaccine. An attempt to review the literature on periodontal vaccine, including active immunization: Whole bacterial cells, sub-unit vaccines, synthetic peptides as antigens; passive immunization: Murine monoclonal antibodies and plantibodies; and genetic immunization: Plasmid vaccines, live, viral vector vaccines, has been done in this study.
|How to cite this article:|
Gupta C, Deepa D. Periodontal vaccine: A new vista in periodontology - A review.J Curr Res Sci Med 2016;2:10-13
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Gupta C, Deepa D. Periodontal vaccine: A new vista in periodontology - A review. J Curr Res Sci Med [serial online] 2016 [cited 2020 Apr 3 ];2:10-13
Available from: http://www.jcrsmed.org/text.asp?2016/2/1/10/184117
Periodontitis is a disease of multifactorial origin, "an inflammatory disease of the teeth caused by specific microorganisms or group of microorganisms, resulting in progressive destruction of the periodontal ligament and alveolar bone with pocket formation, recession, or both."  The current concept on the etiology of periodontitis considers three groups of factors that determine whether active periodontitis will occur in patients: Susceptible host, presence of pathogenic species and the absence, or a small proportion of "beneficial bacteria." The current treatment of periodontitis is nonspecific and is centered on the removal of supragingival and subgingival plaque by mechanical debridement and surgical procedures. Due to its high prevalence rate, this disease has created an innovative interest to find a solution in the form of vaccine. 
Vaccination is induction of immunity by injecting a dead or attenuated form of pathogen.  The first vaccine, named after vaccinia, the cow pox virus was pioneered by Jenner 200 years ago. It was the first deliberate scientific attempt to prevent an infectious disease (small pox).  Effective vaccines have successfully eradicated or significantly reduced the prevalence of several diseases, especially in developed countries.  Recent advances in cellular and molecular biology have led to the development of new strategies for vaccines against many types of infectious diseases. With the rapid growth of microbial genome sequencing and bioinformatics analysis tools, we have the potential to examine all the genes and proteins from any human pathogen. These techniques have the capability to provide us with new targets for antimicrobial drugs and vaccines.  Among some 300 species of bacteria involved in subgingival plaque, 5-7 species have been implicated in the etiology of periodontitis, but one or two species - Porphyromonas gingivalis or Tannerella forsythia (formerly, Bacteroides forsythus) - might play an important role as primary pathogens.  In the early 20 th century, three periodontal vaccines were employed: Pure cultures for streptococcus and other microorganisms, autogenous vaccines, and stock vaccines. Example includes Vancott's vaccine and Inava endocarp vaccine. The mechanisms of action of periodontal immunization are active immunization - whole bacterial cells, sub-unit vaccines, synthetic peptides as antigens; passive immunization - murine monoclonal antibodies and plantibodies; genetic immunization - plasmid vaccines, live, and viral vector vaccines.  In this article, an attempt is made to review the literature available on periodontal vaccine.
The need for vaccine development arose because of bacteria which are capable of evading host immune responses and invading the tissues, such as P. gingivalis, which produces protease that not only provides peptides needed for its propagation but also degrades serum-antibacterial components and immune cell-derived peptides, enabling it to hide from the elements of local gingival immune system by invading epithelial cells. It can then escape into the systemic circulation by invading endothelial cells. To decrease the incidence of periodontal disease-related systemic disease, periodontal treatment puts a financial burden on the individuals suffering from it. 
Studies in primates have suggested that it is possible to reduce the gingival colonization of some putative pathogens by immunization. , Availability of a periodontal vaccine would not only prevent or modulate the course of periodontal disease but also enhance the quality of life of people for whom periodontal treatment could not be easily obtained. 
Recently, a variety of strategies to enhance the immunogenicity of antigenic components of B- or T-lymphocytes have been adopted in vaccine trials against periodontal disease. These include, but not limited to, immunization of dendritic cells pulsed with antigens, the use of improved adjuvant formulas (e.g., the use of alum as an alternative to heat shock protein [HSP]-based adjuvant), the use of recombinant plant monoclonal antibodies (plantibodies), and the use of transgenic microorganisms as antigen vectors.  Three types of vaccines were employed for the control of periodontal diseases.  These include the vaccines prepared from pure cultures of streptococci and other oral organisms; autogenous vaccines; stock vaccines such as Vancott's vaccine, Goldenberg's vaccine, or Inava endocarp vaccine.
The study of periodontal disease in humans has been of considerable interest throughout the past decades.  In 1996, the consensus report of the World Workshop on Clinical Periodontics concluded that three bacterial species, P. gingivalis, Aggregatibacter actinomycetemcomitans, and T. forsythia, should be considered as the major periodontal pathogens.  Periodontal immunotherapy is indicated for severe periodontal disease with loss of bone around teeth, inflammation, and association with oral bacterial infection below gingival line, exacerbated diabetes and cardiovascular disease, and where mouth rinses do not work.  Immunization using a vaccine against periodontitis decreases the number of periodontopathic bacteria in the subgingival flora and inhibits alveolar bone destruction in several animal models. The foremost step in vaccine development is identification of an antigenic component from various organisms that could provide immune protection. Identification of such an antigen is made difficult by the fact that the periodontopathic species have a complex clonal structure with multiple serotypes, and no single type or groups of types have been documented to cause human periodontitis.  The significance of periodontal vaccine development would be to eradicate the global periodontal disease burden with the ultimate purpose of lowering periodontal disease-associated morbidity in humans. The role of any vaccine, however, should also be seen within the context of changes in lifestyle. The vaccine effect should be seen to enhance the feasibility of maintaining oral health and to maximize retention of the natural dentition, thus minimizing the need for prosthetic or implant restorations in the oral cavity. Moreover, recent novel findings linking periodontitis and systemic health concerns (atherosclerosis, diabetes mellitus, preterm low-weight birth, rheumatoid arthritis, etc.) would suggest that prevention or treatment of periodontal diseases is fundamental to the effective management of atherosclerosis, uncontrolled diabetes, and low-weight preterm birth or preeclampsia.  Vaccination may be an important adjunctive therapy to mechanical debridement in humans to prevent colonization by periopathogens. When present in subgingival plaque as an undisturbed biofilm, specific antibodies restrict the progression of disease by blocking penetration into gingival tissue and neutralizing key virulence factors associated with acquisition of essential nutrients.  Various forms of active and passive immunization methods have been tried. Although most of these studies have yielded encouraging results, none of these modalities of immunization have been able to be incorporated as a sole or complete "vaccine" against periodontal disease for use in the human population as yet.  Other preventive strategies employed for periodontal disease are use of probiotics-live microorganisms administered in adequate amount conferring beneficial health effect on host;  gene therapy - insertion of genes into an individual's cells and tissue to treat a disease. 
AN UPDATE ON EXPERIMENTS RELATED TO PERIODONTAL VACCINE
Hardham et al.  conducted a study to evaluate the immunogenic properties and vaccine performance of a monovalent canine periodontal disease vaccine in the mouse oral challenge model of periodontitis. They prepared experimental vaccines from formalin, heat, or aeration-inactivated cultures of Porphyromonas gulae B43. Based on the results of the study, the authors concluded that a periodontal vaccine may be a useful tool in preventing the progression of periodontitis in animals. Lee et al.  conducted a study to evaluate the performance of P. gingivalis HSP60 as a vaccine candidate. Rats were immunized with P. gingivalis HSP60, and experimental alveolar bone loss was induced by the infection with multiple periodontopathogenic bacteria. Results showed a very strong inverse relationship between postimmune anti-P. gingivalis HSP immunoglobulin G (IgG) levels and the amount of alveolar bone loss induced by either P. gingivalis or multiple bacterial infection. Genco et al.  studied the effects of immunization with invasive or noninvasive P. gingivalis strains on the pathogenesis of infection in a mouse chamber model. They concluded that immunization with invasive P. gingivalis A7436 and W83 or noninvasive P. gingivalis 33277, HG405, and 381 protected mice from secondary lesion formation and death after challenge with invasive P. gingivalis A7436 or W83. P. gingivalis-specific antibody did not, however, inhibit the colonization of P. gingivalis within chambers. Miyachi et al.  conducted a study to clarify the effect of arginine-specific-gingipain A (rgpA), a DNA vaccine that could prevent alveolar bone loss in mice. The results of this study suggested that immunization with rgpA DNA vaccine via the nasal cavity is an effective method for preventing alveolar bone loss incurred by infection with P. gingivalis. Yonezawa et al.  in their study evaluated the protective potential of rgpA DNA vaccine against a lethal challenge of P. gingivalis and also analyzed the induction of cellular immune responses by the DNA vaccine. Based on the results, it appeared that immunization with the rgpA DNA vaccine may induce both humoral and cellular immune responses for protection against P. gingivalis challenge, further demonstrated that attenuated excessive interferon-γ production in animals immunized with an rgpA DNA vaccine may play a key role in protection against P. gingivalis infection. DeCarlo et al.  conducted an experiment in a rat periodontitis model to investigate the use of P. gingivalis binding domain, recombinant heme acquisition rHA2 as an immunogen for periodontitis vaccine. It was concluded that subcutaneous administration of rHA2, without addition of adjuvant, stimulated an immune response which was significant enough to provide some clinical protection from periodontitis. Choi et al.  studied the effect of immunization with a P. gingivalis fimbrial protein, a capsular polysaccharide (CPS), or a CPS-fimbrial protein conjugate vaccine and compared their effects in human peripheral blood lymphocytes severe combined immunodeficiency mice. They concluded that CPS-fimbrial protein conjugated from P. gingivalis could potentially be developed as a vaccine against periodontal infection by P. gingivalis. Houri-Haddad et al.  conducted a study to test the hypothesis that different adjuvants in P. gingivalis vaccines would differentially modify the host response to a live P. gingivalis infection. Results showed that vaccination with P. gingivalis in alum attenuated the pro-inflammatory cytokine levels at the site of infection, while the vaccine containing incomplete Freund's adjuvant did the opposite. Although both vaccines induced a similar humoral IgG response, P. gingivalis-induced abscesses were significantly smaller in the alum-adjuvant group. Therefore, the authors concluded that the immune response and the resultant protection to a P. gingivalis infection, in P. gingivalis-vaccinated mice, are adjuvant-dependent. O'Brien-Simpson et al.  conducted a study to show that P. gingivalis W50 whole cells exhibit the same binding pattern to fibrinogen, fibronectin, hemoglobin, and collagen Type V as the arginine- and lysine-specific cysteine protease complex (RgpA-Kgp complex), which binds to these proteins with nanomolar dissociation constants. They also showed that the adhesins of the RgpA-Kgp complex are important in providing protection in the murine lesion and periodontitis models when the complex is used as a vaccine and that the immune response is predominately a Th2 response. The results suggested that when the RgpA-Kgp complex or functional binding motif, or active site peptides are used as a vaccine, they induce a Th2 response that blocks function of the RgpA-Kgp complex and protects against periodontal bone loss. According to Evans et al.,  there are differing opinions on whether mucosal or systemic antibody responses are important for protection against periodontal disease. For the most part, immunization with appropriate antigens leading predominantly toward either type of humoral response has resulted in significant protection. Herminajeng et al. found that mice immunized with antisurface-associated material from A. actinomycetemcomitans exhibited a rise in protective antibody levels acting as an opsonin. 
Periodontitis is a chronic inflammatory disease of the supporting structures of the teeth with multifactorial disease involving plaque and calculus, systemic and genetic factors. The elucidation of the specific bacterial etiology of periodontitis suggests that the development of specific treatment modality to target site colonization or virulence of P. gingivalis and A. actinomycetemcomitans is now a more rational approach to treat disease. Various forms of active and passive immunization methods have been tried. Researches are still carried out to unravel the mystery with humans, as none of the modalities have been able to be incorporated as a sole or complete "vaccine" against periodontal disease.
The development of vaccine is dependent on the identification of bacterial antigens that are expressed in vivo and induction of a protective response. DNA vaccines that were described <5 years ago have already progressed to Phase I clinical trial in healthy humans.
Although success has been achieved in the case of animal models, there are several reasons which still have to be overcome to make the dream of periodontal vaccine for humans a reality. Some of the reasons include complexity and uncertainty of the different forms of periodontal diseases; difficulty in accurately differentiating between primary colonizers and secondary invaders; relative difficulty in growing and identifying many of the disease-associated microorganisms; and the variability of the plaque composition from one individual to the other and between sites in the same individual. Thus, the current status of our understanding in the field of vaccines against periodontal disease is not complete, but extensive research in this direction may hold a promising future in the development of periodontal vaccine.
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Conflicts of interest
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