Passive Immunization Against Dental Caries and Periodontal Disease: Development of Recombinant and Human Monoclonal Antibodies

Abstract

Indigenous micro-organisms in the oral cavity can cause two major diseases, dental caries and periodontal diseases. There is neither agreement nor consensus as to the actual mechanisms of pathogenesis of the specific virulence factors of these micro-organisms. The complexity of the bacterial community in dental plaque has made it difficult for the single bacterial agent of dental caries to be determined. However, there is considerable evidence that Streptococcus mutans is implicated as the primary causative organism of dental caries, and the cell-surface protein antigen (SA I/Il) as well as glucosyltransferases (GTFs) produced by S. mutans appear to be major colonization factors. Various forms of periodontal diseases are closely associated with specific subgingival bacteria. Porphyromonas gingivalis has been implicated as an important etiological agent of adult periodontitis. Adherence of bacteria to host tissues is a prerequisite for colonization and one of the important steps in the disease process. Bacterial coaggregation factors and hemagglutinins likely play major roles in colonization in the subgingival area. Emerging evidence suggests that inhibition of these virulence factors may protect the host against caries and periodontal disease. Active and passive immunization approaches have been developed for immunotherapy of these diseases. Recent advances in mucosal immunology and the introduction of novel strategies for inducing mucosal immune responses now raise the possibility that effective and safe vaccines can be constructed. In this regard, some successful results have been reported in animal experimental models. Nevertheless, since the public at large might be skeptical about the seriousness of oral diseases, immunotherapy must be carried out with absolute safety. For this goal to be achieved, the development of safe antibodies for passive immunization is significant and important. In this review, salient advances in passive immunization against caries and periodontal diseases are summarized, and the biotechnological approaches for developing recombinant and human-type antibodies are introduced. Furthermore, our own attempts to construct single-chain variable fragments (ScFv) and human-type antibodies capable of neutralizing virulence factors are discussed.

Effects of egg yolk antibody against Porphyromonas gingivalis gingipains in periodontitis patients

“…been reported in a rat model (35,36) and in human subjects (2). However, due to the difficulties associated with developing effective animal models and the multifaceted nature of periodontitis, passive immunization therapy against periodontitis has not been studied extensively (37). Gingipains degrade cytokines (10,11), components of the complement system (8,9), and several receptors, including macrophage CD14 (13,14,38) and T-cells CD4 and CD8 (39), thereby perturbing the host defense system and facilitating sustained colonization of P. gingivalis.…”

Targeted Antimicrobial Therapy Against Streptococcus mutans Establishes Protective Non‐cariogenic Oral Biofilms and Reduces Subsequent Infection

“…Numerous approaches include the development of anticaries vaccines against either cell surface antigens (Abiko, 2000) or a glucosyltransferase enzyme that is responsible for glucan production (Xu et al, 2007). In an effort to reduce acid production of naturally occurring S. mutans, replacement therapy using a genetically engineered S. mutans that is able to outcompete indigenous strains while producing significantly less acid has been attempted (Hillman et al, 2000).…”

Molecular Genetic Analysis of the Virulence of Oral Bacterial Pathogens: An Historical Perspective

“…This review will not survey this area of research in detail, and the reader should refer to several recent comprehensive reviews of this subject for a broader perspective (Abiko, 2000;Michalek et al, 2001). Despite the fact that anticaries vaccines have been demonstrated to be effective in animal models (Smith and Taubman, 1995), they have not yet been examined in human trials.…”