Abstract
BackgroundWe previously demonstrated that nasal administration of periodontitis gene vaccine (pVAX1-HA2-fimA) or pVAX1-HA2-fimA plus IL-15 as adjuvant provoked protective immunity in the periodontal tissue of SD rats. This study evaluated the immune effect of pVAX1-HA2-fimA plus CpG-ODN 1826 as an adjuvant in the SD rat periodontitis models to improve the efficacy of the previously used vaccine.MethodsPeriodontitis was induced in maxillary second molars in SD rats receiving a ligature and infected with Porphyromonas gingivalis. Forty-two SD rats were randomly assigned to six groups: A, control without P. gingivalis; B, P. gingivalis with saline; C, P. gingivalis with pVAX1; D, P. gingivalis with pVAX1-HA2-fimA; E, P. gingivalis with pVAX1-HA2-fimA/IL-15; F, P. gingivalis with pVAX1-HA2-fimA+CpG ODN 1826 (30 µg). The levels of FimA-specific and HA2-specific secretory IgA antibodies in the saliva of rats were measured by ELISA. The levels of COX-2 and RANKL were detected by immunohistochemical assay. Morphometric analysis was used to evaluate alveolar bone loss. Major organs were observed by HE staining.Results30 μg could be the optimal immunization dose for CpG-ODN 1826 and the levels of SIgA antibody were consistently higher in the pVAX1-HA2-fimA+CpG-ODN 1826 (30 µg) group than in the other groups during weeks 1–8 (P < 0.05, except week 1 or 2). Morphometric analysis demonstrated that pVAX1-HA2-fimA+CpG-ODN 1826 (30 µg) significantly reduced alveolar bone loss in ligated maxillary molars in group F compared with groups B–E (P < 0.05). Immunohistochemical assays revealed that the levels of COX-2 and RANKL were significantly lower in group F compared with groups B–E (P < 0.05). HE staining results of the major organs indicated that pVAX1-HA2-fimA with or without CpG-ODN 1826 was not toxic for in vivo use.ConclusionsThese results indicated that CpG-ODN 1826 (30 µg) could be used as an effective and safe mucosal adjuvant for pVAX1-HA2-fimA in SD rats since it could elicit mucosal SIgA responses and modulate COX-2 and RANKL production during weeks 1–8, thereby inhibiting inflammation and decreasing bone loss.
Highlights
We previously demonstrated that nasal administration of periodontitis gene vaccine or pVAX1-HA2-fimA plus IL-15 as adjuvant provoked protective immunity in the periodontal tissue of Sprague Dawley (SD) rats
Periodontitis gene vaccine‐induced salivary secretory IgA antibodies expression The levels of FimA-specific and HA2-specific secretory IgA antibodies in the saliva of rats in groups I-VI were measured by ELISA from week 0 to 10, and the results showed that the levels of SIgA antibody in all groups, except the blank group, started to increase from week 1, reached the highest level at week 5 or week 6, and started to decrease (Fig. 3a, b)
The mean distance between the enamel-cement junction and the alveolar bone crest was 503.44 ± 49.46 μm and 481.77 ± 17.12 μm in the second maxillary molars in groups D and group E, respectively (Fig. 5d, e). pVAX1-HA2-fimA+CpG oligodeoxynucleotide (CpG-ODN) 1826 (30 μg) significantly reduced alveolar bone loss in ligated maxillary molars in group F compared with groups B–E (P < 0.05) (Fig. 5g)
Summary
We previously demonstrated that nasal administration of periodontitis gene vaccine (pVAX1-HA2-fimA) or pVAX1-HA2-fimA plus IL-15 as adjuvant provoked protective immunity in the periodontal tissue of SD rats. Multiple studies have demonstrated that P. gingivalis could produce many virulent factors, such as gingipains, lipopolysaccharide (LPS), and fimbriae/pili, to destruct the periodontal tissue on their own or act through other mediators to induce inflammation [6, 7]. The polymer of the fimA protein (fimbrillin), encoded by the gene fimA, is an important virulence factor of P. gingivalis [11,12,13]. It plays an important role in the pathogenesis of P. gingivalis, which is closely related to periodontitis [14]
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