In conclusion, the present investigation demonstrated that CpG-ODN 1826 (30 μg) could be used as an effective and safe mucosal adjuvant for periodontitis gene vaccine (pVAX1-HA2-fimA) since it could elicit mucosal SIgA responses and modulate COX-2 and RANKL production, thereby inhibiting inflammation and decreasing bone loss. Here, PTGS2 is linked to periodontitis.