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.