A targeted fimA DNA vaccine prevents alveolar bone loss in mice after intra-nasal administration.
OBJECTIVE
To construct a dendritic cell (DC)-targeted DNA vaccine against FimA of Porphyromonas gingivalis and evaluate the immunogenicity and protection in mice.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. ymai016@yahoo.com.cn
Fei
F
Yu
Qing-An
QA
Xu
Weimin
W
Chen
D000281:Administration, Intranasal; D016301:Alveolar Bone Loss / Q000517:prevention & control*; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000097:blood / Q000276:immunology; D015703:Antigens, CD / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage; D060908:CTLA-4 Antigen; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D036781:Fimbriae Proteins / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000032:analysis; D007141:Immunoglobulin Fc Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000032:analysis / Q000097:blood; D007142:Immunoglobulin gamma-Chains / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018933:Pili, Sex / Q000276:immunology*; D010957:Plasmids; D016966:Porphyromonas gingivalis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012463:Saliva / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage
D000907:Antibodies, Bacterial; D015703:Antigens, CD; D001428:Bacterial Vaccines; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C556707:Ctla4 protein, mouse; D007071:Immunoglobulin A, Secretory; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; C063055:fimbrillin; D036781:Fimbriae Proteins