HGP44 reduces Porphyromonas gingivalis–induced alveolar bone loss in mice

Objectives: Porphyromonas gingivalis is a major pathogen of chronic periodontitis, and one of its major virulence factors, arg-gingipain A (RgpA), is closely associated with the induction of periodontal inflammation by this microorganism. RgpA consists of a preproprotein, a catalytic domain and an adhesin/hemagglutinin (HGP) domain. In the present study, we investigated the immunogenic effect of rgpA-domain DNA vaccines and their ability to induce a protective effect against alveolar bone loss induced by P. gingivalis infection, with the aim of clarifying their potential as candidate antigens for a new vaccine.

Methods: We constructed DNA vaccine plasmids expressing the catalytic domain (pCAT), HGP44 and HGP15-27 of rgpA. BALB/c mice were immunized with these DNA vaccines by a Gene Gun, weekly for 7 weeks. Levels of antibodies against RgpA were determined by ELISA. Six weeks after the first immunization, the mice were given 5 mg each of kanamycin and ampicillin by gavage, once a day for 4 days, and after a 3-day antibiotic-free period, were infected orally with 1×10¹⁰ CFU of P. gingivalis ATCC33277. Alveolar bone loss was assessed by measuring the distance from the alveolar bone crest to the cemento-enamel junction of the maxillary molars in each mouse.

Results: Antibody titers in the sera from mice immunized with pHGP44 were the highest among the rgpA-domain DNA vaccines. Antibody levels induced by pHGP44 were almost the same as those obtained with the rgpA DNA vaccine, suggesting that HGP44 has high immunogenicity. Alveolar bone loss was reduced significantly in both the rgpA DNA vaccine-immunized group and the HGP44-immunized group (p<0.01), whereas the pCAT-and pHGP15-27-immunized groups showed no protection against alveolar bone loss. Conclusions: The results revealed that pHGP44 had strong immunogenicity, suggesting that it has the ability to induce protective immunity against alveolar bone loss induced by P. gingivalis infection.