Abstract:

Objective To immunize pristane-induced BALB/c mouse models for lupus with MCP-1 DNA vaccine, and to study the immunosuppressive effect and protective effect on kidney of the DNA vaccine in the murine lupus model. Methods BALB/c mice were randomly divided into four groups. Pristane-induced lupus mice were immunized with MCP-1 DNA vaccine （MCP-1 vaccine group）, empty plasmids （empty plasmid control group） or remained non-vaccinated (lupus model group). Normal mice receiving neither induction nor vaccination served as the normal control. Subsequently, mice were monitored for body weight and 24-hour protein excretion; ELISA was used to measure the serum levels of MCP-1antibody and antigen, and immunofluorescence method to detect serum ANA. Hematoxylin and eosin staining was performed to observe pathological changes of murine kidney, immunohistochemistry to assess the expression of CD68 and MCP-1 in renal tissue. Results At week 24, there was a significant difference in body weight and 24-hour protein excretion among the 4 groups （F = 20.31, 6.74, both P < 0.05）, and LSD test showed that MCP-1 vaccine group differed significantly from the model group and empty plasmid group in the two parameters （both P < 0.01）. The serum levels at week 24 were （572.6 ± 58.55） ng/L, （169.52 ± 28.71） ng/L, （601.98 ± 83.43） ng/L and（61.11 ± 66.12） ng/L for MCP-1 antigen （F = 143.09, P < 0.05）, （357.88 ± 82.41） ng/L, （770.14 ± 220.91） ng/L, （294.25 ± 177.22） ng/L and （129.73 ± 168.24） ng/L for MCP-1 antibody （F = 15.81, P < 0.01） in lupus model group, MCP-1 vaccine group, empty plasmid group and normal control group, respectively; LSD test revealed that the MCP-1 vaccine group was significantly different from the lupus model group and empty plasmid group in the serum level of MCP-1 antigen and from the other 3 groups in the level of MCP-1 antibody （all P < 0.01）. No significant difference was observed in the positivity rate of antinuclear antibody among the 4 groups. In MCP-1 vaccine group and normal control group, renal damage was much milder together with a reduction in the number of MCP-1- and CD68-positive cells in renal tissue in comparison with the other two groups. Conclusion MCP-1 DNA vaccines can efficiently inhibit the expression of MCP-1 antigen and induce the production of MCP-1 antibody in mouse model for lupus.

Key words: Key words: lupus erythematosus, systemic, DNA vaccine, MCP-1