Human TNF-alpha gene vaccination prevents collagen-induced arthritis in mice

Abstract

TNFα is a key factor in the pathogenesis of rheumatoid arthritis. To investigate whether heterologous TNFα gene vaccination could induce anti-TNFα antibodies via cross-reaction and prevent the inflammatory arthritis, we constructed two plasmids by inserting a full-length cDNA of human TNFα into a secreted vector (pSecTag-TNFα) and a non-secreted vector (pTARGE-TNFα), respectively. Administering either plasmid to collagen-induced arthritis (CIA) mice reduced paw swelling and synovium-infiltrating inflammatory cells. This reduction was accompanied by down-regulated TNFα in sera and joints. The spleen cells from treated CIA mice displayed decreased IFN-γ mRNA levels and matrix metalloproteinase-9 bioactivity in comparison with those from CIA control. Furthermore, both spontaneous and collagen-specific proliferation of the lymphocytes was significantly decreased after treatment. Administration of plasmids led to an elicited production of antibodies to both human and mouse TNFα. These results suggest that human TNFα gene vaccination prevents CIA in mice likely by inducing cross-reactive antibodies against TNFα, and that heterologous gene vaccination might provide an effective therapeutic strategy to battle TNFα mediated diseases.