A Flagellin-Adjuvanted Trivalent Mucosal Vaccine Targeting Key Periodontopathic Bacteria

oleh: Vandara Loeurng, Sao Puth, Seol Hee Hong, Yun Suhk Lee, Kamalakannan Radhakrishnan, Jeong Tae Koh, Joong-Ki Kook, Joon Haeng Rhee, Shee Eun Lee

Format: Article
Diterbitkan: MDPI AG 2024-07-01

Deskripsi

Periodontal disease (PD) is caused by microbial dysbiosis and accompanying adverse inflammatory responses. Due to its high incidence and association with various systemic diseases, disease-modifying treatments that modulate dysbiosis serve as promising therapeutic approaches. In this study, to simulate the pathophysiological situation, we established a “temporary ligature plus oral infection model” that incorporates a temporary silk ligature and oral infection with a cocktail of live <i>Tannerella forsythia</i> (<i>Tf</i>), <i>Pophyromonas gingivalis</i> (<i>Pg</i>), and <i>Fusobacterium nucleatum</i> (<i>Fn</i>) in mice and tested the efficacy of a new trivalent mucosal vaccine. It has been reported that <i>Tf</i>, a red complex pathogen, amplifies periodontitis severity by interacting with periodontopathic bacteria such as <i>Pg</i> and <i>Fn</i>. Here, we developed a recombinant mucosal vaccine targeting a surface-associated protein, BspA, of <i>Tf</i> by genetically combining truncated BspA with built-in adjuvant flagellin (FlaB). To simultaneously induce <i>Tf</i>-, <i>Pg</i>-, and <i>Fn</i>-specific immune responses, it was formulated as a trivalent mucosal vaccine containing <i>Tf</i>-FlaB-tBspA (BtB), <i>Pg</i>-Hgp44-FlaB (HB), and <i>Fn</i>-FlaB-tFomA (BtA). Intranasal immunization with the trivalent mucosal vaccine (BtB + HB + BtA) prevented alveolar bone loss and gingival proinflammatory cytokine production. Vaccinated mice exhibited significant induction of <i>Tf-</i>tBspA-, <i>Pg-</i>Hgp44-, and <i>Fn-</i>tFomA-specific IgG and IgA responses in the serum and saliva, respectively. The anti-sera and anti-saliva efficiently inhibited epithelial cell invasion by <i>Tf</i> and <i>Pg</i> and interfered with biofilm formation by <i>Fn</i>. The flagellin-adjuvanted trivalent mucosal vaccine offers a novel method for modulating dysbiotic bacteria associated with periodontitis. This approach leverages the adjuvant properties of flagellin to enhance the immune response, aiming to restore a balanced microbial environment and improve periodontal health.