Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
J Clin Periodontol. 2011 Apr;38(4):334-40. doi: 10.1111/j.1600-051X.2010.01700.x. Epub 2011 Jan 24.
To construct a dendritic cell (DC)-targeted DNA vaccine against FimA of Porphyromonas gingivalis and evaluate the immunogenicity and protection in mice.
A targeted DNA plasmid pCTLA4-FimA, which encodes the signal peptide and extracellular regions of mouse cytotoxic T lymphocyte-associated antigen 4 (CTLA4), the hinge and Fc regions of human Igγ1 and FimA of P. gingivalis, was constructed. Mice were immunized with pCTLA4-FimA, the non-targeted DNA plasmid pFimA, which contains only fimA gene, or pCI vector intra-nasally. Serum and saliva antibody responses were detected by enzyme-linked immunosorbent assay. The protection against P. gingivalis-induced periodontitis was evaluated by measuring alveolar bone loss in mice.
Mice immunized with pCTLA4-FimA showed elevated levels of specific serum IgG and salivary IgA antibody responses compared with mice immunized with pFimA (p<0.01). Both pFimA and pCTLA4-FimA immunized groups showed significantly lower alveolar bone loss, with the magnitude protection greater in the latter (p<0.01), compared with the pCI immunized group.
The DC-targeted DNA construct pCTLA4-FimA enhanced both systemic and mucosal immunity following intra-nasal immunization. A DNA-based immunization strategy may be an effective way to attenuate periodontitis induced by P. gingivalis.
构建靶向牙龈卟啉单胞菌 FimA 的树突状细胞(DC)DNA 疫苗,并评估其在小鼠中的免疫原性和保护作用。
构建靶向 DNA 质粒 pCTLA4-FimA,其编码小鼠细胞毒性 T 淋巴细胞相关抗原 4(CTLA4)的信号肽和细胞外区、人 Igγ1 的铰链和 Fc 区以及牙龈卟啉单胞菌的 FimA。通过鼻腔内免疫 pCTLA4-FimA、仅含有 fimA 基因的非靶向 DNA 质粒 pFimA 或 pCI 载体,对小鼠进行免疫。通过酶联免疫吸附试验检测血清和唾液抗体反应。通过测量小鼠牙槽骨丢失来评估针对牙龈卟啉单胞菌诱导的牙周炎的保护作用。
与 pFimA 免疫组相比,pCTLA4-FimA 免疫组小鼠显示出更高水平的特异性血清 IgG 和唾液 IgA 抗体反应(p<0.01)。与 pCI 免疫组相比,pFimA 和 pCTLA4-FimA 免疫组的牙槽骨丢失均显著降低,后者的保护作用更大(p<0.01)。
经鼻腔内免疫后,靶向 DC 的 DNA 构建体 pCTLA4-FimA 增强了系统和黏膜免疫。基于 DNA 的免疫策略可能是减轻牙龈卟啉单胞菌引起的牙周炎的有效方法。