scholarly journals A Porphyromonas gingivalis Capsule-Conjugate Vaccine Protects From Experimental Oral Bone Loss

2021 ◽  
Vol 2 ◽  
Author(s):  
Fernanda G. Rocha ◽  
Aym Berges ◽  
Angie Sedra ◽  
Shirin Ghods ◽  
Neeraj Kapoor ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Conjugate Vaccine ◽  
Porphyromonas Gingivalis ◽  
Capsular Polysaccharide ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Bone Destruction ◽  
Effective Vaccine ◽  
Preclinical Model

Periodontal diseases are chronic inflammatory diseases of the periodontium that result in progressive destruction of the soft and hard tissues supporting the teeth, and it is the most common cause of tooth loss among adults. In the US alone, over 100 million individuals are estimated to have periodontal disease. Subgingival bacteria initiate and sustain inflammation, and, although several bacteria have been associated with periodontitis, Porphyromonas gingivalis has emerged as the key etiological organism significantly contributing to the disease. Currently, intensive clinical maintenance strategies are deployed to mitigate the further progression of disease in afflicted individuals; however, these treatments often fail to stop disease progression, and, as such, the development of an effective vaccine for periodontal disease is highly desirable. We generated a conjugate vaccine, comprising of the purified capsular polysaccharide of P. gingivalis conjugated to eCRM®, a proprietary and enhanced version of the CRM197 carrier protein with predetermined conjugation sites (Pg-CV). Mice immunized with alum adjuvanted Pg-CV developed robust serum levels of whole organism-specific IgG in comparison to animals immunized with unconjugated capsular polysaccharide alone. Using the murine oral bone loss model, we observed that mice immunized with the capsule-conjugate vaccine were significantly protected from the effects of P. gingivalis-elicited oral bone loss. Employing a preclinical model of infection-elicited oral bone loss, our data support that a conjugate vaccine incorporating capsular polysaccharide antigen is effective in reducing the main clinical endpoint of periodontal disease—oral bone destruction. Further development of a P. gingivalis capsule-based conjugate vaccine for preventing periodontal diseases is supported.

scholarly journals DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF MICROBIAL FLORA IMBALANCE IN GINGIVAL BIOFILM

2020 ◽  
Vol 5 (2) ◽  
pp. 76-82
Author(s):  
G. A. Loban ◽  
T. O. Petrushanko ◽  
V. V. Chereda ◽  
M. O. Faustova ◽  
M. M. Ananieva ◽  
...  
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Prognostic Significance ◽  
Fluid Composition ◽  
Dental Tissues ◽  
Periodontal Tissues ◽  
Dmf Index ◽  
Increased Risk ◽  
Hard Dental Tissues

Background. Periodontal tissues inflammatory diseases are widespread among young people. Objective. This study was aimed at elaborating the method to assess risks of periodontal inflammatory diseases and determining its efficacy depending on the state of dental tissues, gum tissues and sex.          Methods. The study included 182 students (93 men, 89 women) aged 19-29: 22 individuals had no lesions of hard dental tissues and no signs of periodontal disease; 51 individuals were found to have DMF index <6; 52 individuals – DMF index ≥6; 57 individuals were diagnosed with chronic catarrhal gingivitis. Primary groups were formed in autumn; re-examination was carried in spring. The research participants were assessed for detection of risks of periodontal inflammatory disease by the method developes by the authors (Patent UA 54041). Results. The study revealed that the risk of development of preiodontitis increases in individuals with high caries and gingivitis intensity. In spring, more individuals suffer from microbial imbalance in in the composition of gingival sulcus fluid and decrease in the mean stability coefficient value that indicates an increased risk of inflammatory periodontal disease development. Women were less likely to experience seasonal dysbiotic changes in the gingival sulcus fluid composition compared with men. Conclusions. The method suggested for assessment of the risk of periodontal inflammatory diseases is of high informativeness. It allows clinicians detecting early pre-nosological signs of oral microbiocenosis imbalance that enhances the effectiveness of early diagnosis of inflammatory periodontal diseases.

scholarly journals Immunological Pathways Triggered byPorphyromonas gingivalisandFusobacterium nucleatum: Therapeutic Possibilities?

2019 ◽  
Vol 2019 ◽  
pp. 1-20 ◽  
Author(s):  
Kívia Queiroz de Andrade ◽  
Cássio Luiz Coutinho Almeida-da-Silva ◽  
Robson Coutinho-Silva
Keyword(s):  
Immune Responses ◽  
Periodontal Disease ◽  
Virulence Factors ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Anaerobic Bacteria ◽  
Fusobacterium Nucleatum ◽  
Host Immune Responses ◽  
Molecular Events ◽  
Survival Studies

Porphyromonas gingivalis(P. gingivalis) andFusobacterium nucleatum(F. nucleatum) are Gram-negative anaerobic bacteria possessing several virulence factors that make them potential pathogens associated with periodontal disease. Periodontal diseases are chronic inflammatory diseases of the oral cavity, including gingivitis and periodontitis. Periodontitis can lead to tooth loss and is considered one of the most prevalent diseases worldwide.P. gingivalisandF. nucleatumpossess virulence factors that allow them to survive in hostile environments by selectively modulating the host’s immune-inflammatory response, thereby creating major challenges to host cell survival. Studies have demonstrated that bacterial infection and the host immune responses are involved in the induction of periodontitis. The NLRP3 inflammasome and its effector molecules (IL-1βand caspase-1) play roles in the development of periodontitis. We and others have reported that the purinergic P2X7 receptor plays a role in the modulation of periodontal disease and intracellular pathogen control. Caspase-4/5 (in humans) and caspase-11 (in mice) are important effectors for combating bacterial pathogens via mediation of cell death and IL-1βrelease. The exact molecular events of the host’s response to these bacteria are not fully understood. Here, we review innate and adaptive immune responses induced byP. gingivalisandF. nucleatuminfections and discuss the possibility of manipulations of the immune response as therapeutic strategies. Given the global burden of periodontitis, it is important to develop therapeutic targets for the prophylaxis of periodontopathogen infections.

scholarly journals SOME ASPECTS OF THE EATIOLOGY OF PARODONTUS DISEASES. (LITERATURE REVIEW)

2018 ◽  
pp. 54-59
Author(s):  
N.N. Saveleva ◽  
I.I. Sokolova ◽  
S.I. German ◽  
T.V. Tomilina
Keyword(s):  
Gastrointestinal Tract ◽  
Periodontal Disease ◽  
Structural Damage ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Clinical Manifestations ◽  
Pathological Process ◽  
Chronic Obstructive ◽  
Internal Organs ◽  
Periodontal Tissues

The review of the scientific literature is devoted to the topical issues of studying the etiology of periodontal diseases, which are one of the most common and complex pathologies of the maxillofacial region. Analysis of recent studies proves a stable relationship between the development of periodontal diseases and disorders in the immune system, the neurohumoral system, metabolic disorders, genetic predisposition, and so on. The article presents the data obtained in the course of studying the literature on the role of disorders in the functioning of individual organs (gastrointestinal tract, liver, lungs, heart, and urinary system) in the development of chronic periodontal diseases. The article notes that the anatomical and physiological proximity of the periodontal and digestive tract tissues, the generality of innervation and humoral regulation create prerequisites for the involvement of periodontal disease in the pathological process in diseases of the gastrointestinal tract. One of the main etiological factors in the development of inflammatory diseases of the gastrointestinal tract and periodontium is Helicobacter pylori, which is found in the loci of the oral cavity: in the oral and gingival fluid, on the mucous membrane of the tongue and cheeks, and in the periodontal pockets. It is pointed out that the liver also occupies a special place in the development of periodontal diseases, which is explained by the performance of its significant functions for the human body: regulatory, metabolic, antitoxic and other. There is evidence that the pathology of periodontal disease plays a leading role in the structure of dental diseases in patients with chronic obstructive pulmonary diseases, which is clinically manifested by symptoms of generalized periodontitis of the І-ІІ degrees of development and its complications - partial or complete secondary adentia, and with tooth preservation - defects in dental series and violations of occlusion, function, aesthetics. Scientists suggest a general biological mechanism for the development of generalized periodontitis and cardiovascular diseases, linking the development of periodontal diseases in patients with cardiovascular pathology with microcirculatory disorders. The dependence of the severity of inflammatory changes in the periodontal tissues on the disturbances of salt metabolism in urolithiasis is proved. The data obtained indicate that diseases of the internal organs contribute to the structural damage of periodontal tissues and they are a risk factor for periodontal diseases, which necessitate the presence of not only theoretical knowledge and practical skills in dentistry, but also their awareness of the features and clinical manifestations of somatic pathology. An urgent and justified step in the treatment of periodontal diseases is also the involvement in the process of rendering complex dental care to internist doctors capable of quickly and qualitatively assessment the condition of the internal organs and the basic systems of the patient's body.

scholarly journals Diabetes mellitus and periodontal diseases: A two way relationship

2021 ◽  
Vol 6 (2) ◽  
pp. 43-56
Author(s):  
Gowhar Nazir ◽  
◽  
Josee Amin ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Periodontal Disease ◽  
Inflammatory Diseases ◽  
Periodontal Diseases ◽  
Systemic Effect ◽  
Diabetic Patients ◽  
Periodontal Infection ◽  
Bidirectional Relationship ◽  
Patients With Diabetes ◽  
Global Health Care

Diabetes mellitus and periodontits are both highly prevalent chronic inflammatory diseases. Both diseases share the same risk factors and are a significant global health care burden adversely affecting the quality of life. Evidence from various studies have demonstrated that diabetes is a major risk factor for periodontal disease and is associated with increased incidence, prevalence and severity of periodontal disease. Hyperglycemia associated with diabetes mellitus results in an increased host immunoinflammatory response which adversely affects the periodontal health. Conversely, periodontits is associated with poor metabolic control in patients with diabetes and increased development of diabetic complications suggesting a bidirectional relationship between the two diseases. Periodontal infection via bacteremia exerts a wide systemic effect by contributing to chronic systemic inflammatory burden worsening diabetic state by increasing insulin resistance. Moreover, studies have demonstrated an improvement in glycemic control following periodontal therapy in prediabetic and diabetic patients with periodontitis.

scholarly journals The Interleukin-17 Receptor Plays a Gender-Dependent Role in Host Protection against Porphyromonas gingivalis-Induced Periodontal Bone Loss

2008 ◽  
Vol 76 (9) ◽  
pp. 4206-4213 ◽  
Author(s):  
Jeffrey J. Yu ◽  
Matthew J. Ruddy ◽  
Heather R. Conti ◽  
Kanitsak Boonanantanasarn ◽  
Sarah L. Gaffen
Keyword(s):  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Alveolar Bone ◽  
Gene Knockout ◽  
Bone Destruction ◽  
Mouse Strains ◽  
Interleukin 17 ◽  
Clinical Safety ◽  
Safety Testing ◽  
Chronic Inflammatory Condition

ABSTRACT Interleukin-17 (IL-17) is a proinflammatory cytokine secreted by the newly described CD4+ Th17 subset, which is distinct from classic Th1 and Th2 lineages. IL-17 contributes to bone destruction in rheumatoid arthritis but is essential in host defense against pathogens that are susceptible to neutrophils. Periodontal disease (PD) is a chronic inflammatory condition initiated by anaerobic oral pathogens such as Porphyromonas gingivalis, and it is characterized by host-mediated alveolar bone destruction due primarily to the immune response. The role of IL-17 in PD is controversial. Whereas elevated IL-17 levels have been found in humans with severe PD, we recently reported that female C57BL/6J mice lacking the IL-17 receptor (IL-17RAKO) are significantly more susceptible to PD bone loss due to defects in the chemokine-neutrophil axis (J. J. Yu, M. J. Ruddy, G. C. Wong, C. Sfintescu, P. J. Baker, J. B. Smith, R. T. Evans, and S. L. Gaffen, Blood 109:3794-3802, 2007). Since different mouse strains exhibit differences in susceptibility to PD as well as Th1/Th2 cell skewing, we crossed the IL-17RA gene knockout onto the BALB/c background and observed a similar enhancement in alveolar bone loss following P. gingivalis infection. Unexpectedly, in both strains IL-17RAKO female mice were much more susceptible to PD bone loss than males. Moreover, female BALB/c-IL-17RAKO mice were defective in producing anti-P. gingivalis immunoglobulin G and the chemokines KC/Groα and MIP-2. In contrast, male mice produced normal levels of chemokines and anti-P. gingivalis antibodies, but they were defective in granulocyte colony-stimulating factor upregulation. This study demonstrates a gender-dependent effect of IL-17 signaling and indicates that gender differences should be taken into account in the preclinical and clinical safety testing of anti-IL-17 biologic therapies.

scholarly journals A Diet Rich in Saturated Fat and Cholesterol Aggravates the Effect of Bacterial Lipopolysaccharide on Alveolar Bone Loss in a Rabbit Model of Periodontal Disease

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1405
Author(s):  
Alfonso Varela-López ◽  
Pedro Bullón ◽  
César L. Ramírez-Tortosa ◽  
María D. Navarro-Hortal ◽  
María Robles-Almazán ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Dietary Habits ◽  
Alveolar Bone ◽  
Periodontal Diseases ◽  
Rabbit Model ◽  
Saturated Fat ◽  
Alveolar Bone Loss ◽  
Standard Diet ◽  
Alcoholic Fatty Liver

Increasing evidence connects periodontitis with a variety of systemic diseases, including metabolic syndrome, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). The proposal of this study was to evaluate the role of diets rich in saturated fat and cholesterol in some aspects of periodontal diseases in a lipopolysaccharide (LPS)-induced model of periodontal disease in rabbits and to assess the influence of a periodontal intervention on hyperlipidemia, atherosclerosis, and NAFLD progression to non-alcoholic steatohepatitis. Male rabbits were maintained on a commercial standard diet or a diet rich in saturated fat (3% lard w/w) and cholesterol (1.3% w/w) (HFD) for 40 days. Half of the rabbits on each diet were treated 2 days per week with intragingival injections of LPS from Porphyromonas gingivalis. Morphometric analyses revealed that LPS induced higher alveolar bone loss (ABL) around the first premolar in animals receiving standard diets, which was exacerbated by the HFD diet. A higher score of acinar inflammation in the liver and higher blood levels of triglycerides and phospholipids were found in HFD-fed rabbits receiving LPS. These results suggest that certain dietary habits can exacerbate some aspects of periodontitis and that bad periodontal health can contribute to dyslipidemia and promote NAFLD progression, but only under certain conditions.

scholarly journals Interdisciplinary cooperation between dentists and endocrinologists for identification and management of diabetes mellitus

2019 ◽  
Vol 22 (1) ◽  
pp. 35-43
Author(s):  
Elena E. Maslak ◽  
Victoria N. Naumova
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Diseases ◽  
Interdisciplinary Collaboration ◽  
Periodontal Diseases ◽  
Interdisciplinary Cooperation ◽  
Dental Patients ◽  
Bidirectional Relationship ◽  
Patients With Diabetes ◽  
Definitive Screening

Background: DM mellitus (DM) leads to worsening periodontal diseases, and in turn the inflammatory diseases of maxillofacial region adversely affect the glycemic control and exacerbate the severity of DM, thereby engendering a vicious cycle that compromises the DM management in patients. Taking account of the bidirectional relationship between DM and periodontal disease, interdisciplinary examination of patients with both DM and periodontal diseases is warranted to improve the health outcomes in patients. Aims: This study aims to evaluate the perceptions of dentists and endocrinologists on the interdisciplinary cooperation for identification and management of patients with DM. Materials and methods: Studying patients knowledge about DM and their compliance in providing endocrinological recommendations, dental screening survey to identify DM risk and signs The research was done in 2015-2016 years using clinical survey (dental status survey), statistical analysis. 432 patients from different dental organizations and 433 doctors (371 dentists and 62 endocrinologists) took part in the research. The research was approved by Regional research ethics committee. The written informed consent was taken from each participant. Results: There was insufficient interdisciplinary collaboration for identification and management of patients with diabetes, and lack of motivation among dental patients to endocrinological survey. Hence, it is important to incorporate definitive screening for risk of DM for patients with inflammatory periodontal disease and include dentists in consultation for patients with DM. The feasibility of statutory determination of collaboration between specialists in identification and management of patients with DM was found, dental lectures are necessary in DM school. Conclusions: Our findings suggest the necessity of including dentists in the standard of medical management of patients with DM and incorporating DM screening by a questionnaire upon dental examination.

scholarly journals Capsular Polysaccharide-Fimbrial Protein Conjugate Vaccine Protects against Porphyromonas gingivalis Infection in SCID Mice Reconstituted with Human Peripheral Blood Lymphocytes

1998 ◽  
Vol 66 (1) ◽  
pp. 391-393 ◽  
Author(s):  
Jeom-Il Choi ◽  
Robert E. Schifferle ◽  
Fuminobu Yoshimura ◽  
Byung-Woo Kim
Keyword(s):  
Conjugate Vaccine ◽  
Porphyromonas Gingivalis ◽  
Capsular Polysaccharide ◽  
Human Peripheral Blood ◽  
Peripheral Blood Lymphocytes ◽  
Scid Mice ◽  
Protein Conjugate ◽  
Periodontal Infection ◽  
Fimbrial Protein

ABSTRACT The effect of immunization with either a Porphyromonas gingivalis fimbrial protein, a capsular polysaccharide, or a capsular polysaccharide-fimbrial protein conjugate vaccine were compared in hu-PBL-SCID mice. A significantly higher human immunoglobulin G antibody response and the highest degree of in vivo protection against bacterial challenge was observed in the group immunized with the conjugate vaccine. It was concluded that capsular polysaccharide-fimbrial protein conjugate from P. gingivalis could potentially be developed as a vaccine against periodontal infection by P. gingivalis.

scholarly journals Submandibular Injection of Indoleamine 2,3-Dioxygenase Galectin-3 Fusion Protein Inhibits and Prevents Periodontal Disease Progression Over 12 Weeks

2021 ◽  
Author(s):  
Fernanda Rocha ◽  
Christina Graves ◽  
Ali Altitinchi ◽  
Shaheen A. Farhadi ◽  
Sabrina L. Macias ◽  
...  
Keyword(s):  
Bone Loss ◽  
Periodontal Disease ◽  
Fusion Protein ◽  
Periodontal Diseases ◽  
Repeated Treatment ◽  
Bacterial Burden ◽  
Mandibular Bone ◽  
Indoleamine 2,3 Dioxygenase ◽  
Galectin 3 ◽  
Therapeutic Administration

A major challenge in the treatment of chronic inflammatory diseases including periodontal diseases is the development of therapeutics to safely and specifically direct resolution of inflammation in a localized manner. Here we demonstrate the efficacy of a novel approach that addresses this unmet clinical need. Using an enzyme fusion protein of indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3) with tissue-anchored and thus localized immunomodulatory properties, we prevented and halted progression of induced polymicrobial periodontal disease. Efficacy was achieved with repeated treatment with IDO-Gal3 and was measured by effects on mandibular bone loss, soft tissue inflammation and local T cell plasticity. Specifically, both prophylactic and therapeutic administration of IDO-Gal3 were effective in reducing vertical mandibular bone loss and loss of mandibular bone volume and bone thickness induced by chronic polymicrobial infection. The efficacy observed is at least in part due to localized regulation of innate immune mediators such as IL-1β, IL-6 and IL-8 as well as chemoattractants including IP-10, MCP-1 and MIP-1α, while enhancing the expression of immunoregulatory cytokines such as IL-10. In addition, IDO-Gal3 treatment suppressed the induction of pathogenic CD4+Th1, CD8+Tc1, CD4+Th1/Th17, and CD8+Tc1/Tc17, while promoting the induction of homeostatic CD4+Th17, CD8+Tc17 and CD4+Tregs. Importantly, the efficacy of prophylactically and therapeutically administered IDO-Gal-3 is not dependent on bacterial burden as there were no appreciable effects on bacterial burden following either method of administration. Lastly, therapeutic rather than prophylactic administration of IDO-Gal3 is most effective in preventing mandibular bone loss through more robust innate and adaptive immune modulation. Together these and our previously published data indicate that therapeutic administration of IDO-Gal3 addresses the clinical needs for adjunctive therapeutics to treat active and/or established periodontal diseases.

scholarly journals Immunization with Porphyromonas gingivalis Capsular Polysaccharide Prevents P. gingivalis-Elicited Oral Bone Loss in a Murine Model

2003 ◽  
Vol 71 (4) ◽  
pp. 2283-2287 ◽  
Author(s):  
Dario Gonzalez ◽  
Arthur O. Tzianabos ◽  
Caroline A. Genco ◽  
Frank C. Gibson
Keyword(s):  
Bone Loss ◽  
Porphyromonas Gingivalis ◽  
Virulence Factor ◽  
Murine Model ◽  
Capsular Polysaccharide ◽  
Vaccine Candidate ◽  
Immunoglobulin M ◽  
Periodontal Pathogen ◽  
Vaccine Potential ◽  
Important Virulence Factor

ABSTRACT The capsular polysaccharide (CPS) of the periodontal pathogen Porphyromonas gingivalis is an important virulence factor for this organism. We purified P. gingivalis CPS, immunized mice with this antigen, and assessed the vaccine potential of P. gingivalis CPS by using the murine oral challenge model. Animals immunized with P. gingivalis CPS developed elevated levels of immunoglobulin M (IgM) and IgG in serum that reacted with whole P. gingivalis organisms. The mice immunized with P. gingivalis CPS were protected from P. gingivalis-elicited oral bone loss. These data demonstrate that P. gingivalis CPS is a vaccine candidate for prevention of P. gingivalis-elicited oral bone loss.

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