Nasal Vaccination with GroEL plus CpG ODN Inhibits <i>P. gingivalis</i>-induced Inflammation and Alveolar Bone Loss

Abstract

The oral cavity is structurally considered to be an organ that provide double layers of protection simultaneously through secretory immunoglobulin A (S-IgA) from mucosal immunity and immunoglobulin (Ig) G antibodies (Abs) from gingival crevicular fluid (1-3). Although immunization via injection can induce an effective immune responses in the systemic immune systems, but not an antigen (Ag)specific mucosal immune responses. Therefore, in order to prevent oral infection, it is ideal to induce mucosal immunity and systemic immunity simultaneously. Chronic periodontitis reduces oral function by causing periodontal tissue destruction and bone resorption. Recently, chronic periodontitis has been reported to cause systemic diseases such as diabetes, aspiration pneumonia, and atherosclerosis, and their relationship has been investigated (4-9). Therefore, prevention of periodontitis is important for oral health and systemic health derived from the oral cavity. Currently 7 to 10 bacterial candidates have been claimed to be putative periodontal pathogens (10, 11). Among them, P. gingivalis is a keystone pathogen that is strongly associated with disease progression of chronic periodontitis. The reason for using GroEL as a vaccine antigen is that is can be found in most putative periodontopathic pathogens, including P.gingivalis, and it was reported to crossreact among bacterial antigens. Thus far, a positive relationship has been observed between levels of saliva IgA directed against GroEL and

Mucosal Vaccination Against Periodontal Disease: Current Status and Opportunities

“…Most PD vaccines targeted Porphyromonas gingivalis, while a few targeted Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, or Eikenella corrodens. All studies found significant increases in antigen-specific antibodies, and those assessing clinical effects also observed reduced pathological manifestations (91,(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115). While these data are encouraging, it should be noted that all but two studies (113,116) used rodents, which have limited translational values.…”

“…Indeed, all eleven preclinical studies that evaluated this reported more dual immunity in the oral cavity after mucosal vaccination compared to systemic vaccination (89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99). Furthermore, several studies reported protection against experimental PD-associated bone loss or gingival swelling/ abscessation by mucosal immunization (91,(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114)(115). While these data support the rationale for mucosal PD vaccines, it must be noted that all but two of these studies used rodent PD models (113,116).…”

“…However, to achieve these responses, intranasally administered vaccines must overcome profuse mucosal secretions, mucociliary clearance, and the relative inefficient uptake of antigens by antigen-presenting cells in the nasal cavity ( 162 ). Therefore, the efficacy of intranasal vaccination is especially dependent on adjuvants, which is highlighted by several studies where the omission of adjuvant resulted in the lack of significant antibody responses ( 97 , 101 , 111 , 146 , 148 ). Furthermore, the intranasal route seems to be the only mucosal vaccination route that tested DNA-based vaccines against PD.…”

“…Concurrent progress in mucosal adjuvant technologies offers additional opportunities for periodontal vaccine development. Most of the reviewed studies used bacterial adjuvants, while only a few evaluated innovative nucleic acid adjuvants ( 93 , 101 , 102 , 104 , 147 , 150 , 151 , 166 ) and cytokine adjuvants ( 89 , 90 , 112 ). These adjuvants should be further assessed, but future studies should also consider particulate adjuvants such as chitosan, virus-like particles, and immune stimulating complexes, and particulate adjuvants such as chitosan.…”

Periodontal vaccines via plantibodies: Bridging the gap between aspiration and achievement

“…By following these steps, a thorough review of the literature on periodontal vaccines was conducted, incorporating both peer-reviewed research and insights from professional sources to provide a comprehensive understanding of the topic. "Plantibodies" [1][2][3][4][5][6][7][8][9][10][11][12][13][14] Represent a novel approach in periodontal vaccination, utilizing plants as bioreactors to produce antibodies against periodontal pathogens. This innovative strategy harnesses the genetic engineering capabilities of plants to express and synthesize specific antibodies, thereby offering a sustainable and cost-effective alternative to traditional antibody production methods.…”