The Experimental Study Of Vaccinated With MCP-1 DNA Vaccine On Lupus Mice

Objective: CC-chemokine-encoding DNA vaccine that introduction of a foreign T helper epitope has been reported to be capable of inducing immunologic memory to corresponding pathogenic self CC-chemokines in animal models of autoimmune disease. This study investigated whether monocyte chemoattractant protein 1 (MCP-1) DNA vaccine could inducing strong neutralizing autoantibody against the pathogenic chemokine MCP-1 sufficiently to be protective in a classically autoimmune model of lupus nephritis(LN).Methods: Mice were pretreated with 0.75%bupivacaine (1μl /g) by intramuscular injection into quadriceps femoris muscle 1 wk before plasmid DNA vaccination. Plasmid DNA (50μg) was injected weekly on four occasions into the same site as bupivacaine. One week after the fourth DNA vaccination, Lupus model was induced by a single abdomen injection of pristine (0.5ml). Animals were divided randomly into four groups: normal control(n=8), MCP-1vaccine(n=8), lupus model(n=8), vector control(n=8). 4 weekly 24hr urinary collection and urinary protein assay . 4 weekly body weight monitored collect blood for anti- MCP-1 antibody titer and MCP-1 antigen titer assay , harvest tissue for histology and immunohistochemistry at week 24. Results:The body weight of mice that were vaccinated with MCP-1 DNA vaccines was significantly higher compared with lupus model and vector control(normal control 25.6±1.0 g, MCP-1 vaccine 24.2±2.3 g, lupus model 17.9±2.7g, vector control 18.0±2.2 g, P <0.05). The 24-hour protein urinary of mice that were vaccinated with MCP-1 DNA vaccines was significantly lower compared with lupus model and vector control (normal control 0.189±0.089mg, MCP-1vaccine 0.218±0.152mg, lupus model 0.696±0.321mg, vector control 0.716±0.452mg, P <0.05). The MCP-1 antigen titer of mice that were vaccinated with MCP-1 DNA vaccines was significantly lower compared with lupus model and vector control(normal control 61.11±66.12 pg/ml, vaccine 169.52±28.71 pg/ml, lupus model 572.6±58.55 pg/ml, vector control 601.98±83.43 pg/ml, P <0.05). The anti- MCP-1 antibody titer of mice that were vaccinated with MCP-1 DNA vaccines was significantly higher compared with each other group(normal control 129.73±168.24 pg/ml, MCP-1 vaccine 770.14±220.91 pg/ml, lupus model 357.88±82.41 pg/ml, vector control 294.25±177.22 pg/ml, P <0.05). Mice that were vaccinated with MCP-1 DNA vaccine developed much less severe renal structural injury at week 24 of lupus mice . Immunohistochemical staining of inflammatory cells revealed that MCP-1 DNA vaccination significantly reduced glomerular macrophage recruitment and MCP-1expression compared with vector control and lupus model.. Conclusion: The protective effect of the modified MCP-1 DNA vaccine was associated with blockade of glomerular and interstitial macrophage recruitment by neutralizing autoantibody against MCP-1, which plays a critical role in eliciting renal injury in lupus nephritis.