Anti-FimA monoclonal antibodies reveal dual roles in porphyromonas gingivalis pathogenesis

Background Porphyromonas gingivalis (P. gingivalis) is a keystone pathogen in periodontitis, a chronic inflammatory disease with systemic links. Its major fimbrial protein, FimA, is essential for bacterial adhesion and co‑aggregation, making it a promising immunotherapeutic target. Although anti-FimA antibodies are detected in patients and correlate with disease severity, their functional roles remain incompletely understood.Objective To generate and functionally characterize FimA-targeting monoclonal antibodies (mAbs) and define their functional impact on P. gingivalis pathogenesis.Design Mice were immunized with recombinant FimA (rFimA) protein to generate hybridomas producing high-affinity mAbs that recognize distinct, non-overlapping epitopes. The functional effects of these mAbs on P. gingivalis adhesion, phagocytosis, complement killing, aggregation and biofilm architecture were evaluated using binding assays, flow cytometry, biolayer interferometry and microscopy.Results A panel of high-affinity anti-FimA mAbs targeting distinct, non-overlapping epitopes was generated. Although all mAbs blocked bacterial adhesion and enhanced phagocytosis, they showed limited complement-dependent killing and, paradoxically, induced aggregation that promoted structured biofilm formation.Conclusion Anti-FimA mAbs exert a dual and opposing functionality, conferring host protection while paradoxically enhancing bacterial persistence through biofilm promotion. These findings reveal a previously unrecognized complexity in anti-FimA humoral immunity and provide important insights for the design of targeted immunotherapies against P. gingivalis infection.