Development of monoclonal antibodies against Mfa1 and their protective capacity in an experimental periodontitis model.

Unlabelled: (), a gram-negative, black-pigmented anaerobe, is a major etiological agent and a leading cause of periodontitis. Fimbriae protein Mfa1 is a key virulence factor of and plays a crucial role in bacterial adhesion, colonization, biofilm formation, and persistent inflammation, making it a promising therapeutic target. However, the role of anti-Mfa1 antibodies and the underlying protective mechanisms remain largely unexplored. Here, we developed and characterized the monoclonal antibodies (mAbs) targeting the Mfa1 protein of . Function analysis showed that anti-Mfa1 mAbs mediated bacterial agglutination and inhibited adhesion to saliva-coated hydroxyapatite and host cells. Notably, anti-Mfa1 mAbs significantly reduced bacterial burden and alveolar bone loss in a -induced experimental periodontitis model. These results show that anti-Mfa1 mAbs can be beneficial in alleviating infections, and provide important insights for the development of adequate adjuvant treatment regimens for Mfa1-targeted therapeutics.

Importance: Fimbriae (pili) play an important role in bacterial adhesion, invasion of host cells and tissues, and formation of biofilms. Studies have shown that two types of fimbriae of , FimA and Mfa1, are important for colonization and infection through their binding to host tissues and other bacteria. While anti-FimA antibodies have been shown to improve periodontitis, the effect of anti-Mfa1 antibodies on infection and periodontitis was previously unknown. In this study, we report for the first time that anti-Mfa1 monoclonal antibodies can reduce infection and improve periodontitis. These findings suggest that Mfa1 represents a promising therapeutic target, and the development of anti-Mfa1 mAbs holds a potential as essential diagnostic and adjunctive therapeutic tools for managing -related diseases.