Immunoprotective effects of a hemin-binding peptide derived from hemagglutinin-2 against infection with Porphyromonas gingivalis

The principal etiologic agent in periodontal disease, Porphyromonas gingivalis, generates cysteine proteases that bind heme with domains such as hemagglutinin-2 (HA2). High-affinity HA2-hemin binding supplies the porphyrin and ferric iron needed for growth and virulence. The DHYAVMISK peptide, recently identified at the hemin-binding site of HA2, inhibits hemin binding. We now evaluate the protective effect of vaccination with DGFPGDHYAVMISK (termed DK) against P. gingivalis using a rat infection model. Rats immunized with DK generated anti-peptide serum IgGs and salivary sIgAs (as measured by ELISA). In a subcutaneous abscess model, the protective effect of immunization was then investigated by measuring abscess size following subcutaneous injection with P. gingivalis. In an oral infection model, a ligature inoculated with P. gingivalis was used to induce periodontitis. The degree of bone erosion, ordinarily provoked by infection, was then evaluated by micro-computed tomography. We found that anti-peptide antibody titers of serum IgGs and salivary sIgAs for rats immunized with DK and adjuvant were significantly higher than for sham-immunized rats (injected with adjuvant/PBS alone; P<.05). In the subcutaneous abscess model, the DK+adjuvant-vaccinated rats recovered faster than sham-vaccinated animals, with their abscess sizes significantly smaller (P<.05). Further, in the experimental periodontitis model, bone loss at the molar palatal side for DK+adjuvant-vaccinated rats was significantly lower than for sham-vaccinated animals (P<.05). Collectively, these data demonstrate the potential of (DK) peptide immunization in terms of eliciting an immunoprotective effect against infection with P. gingivalis.