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

Yan Shen, Jia Chen, Xianming Zhang, Xuefeng Wu, Qiang Xu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1140-1149
Number of pages10
JournalInternational Immunopharmacology
Issue number9
StatePublished - Sep 2007


  • Antibodies
  • Collagen-induced arthritis
  • Cross-reaction
  • Heterologous gene vaccination
  • TNFα

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology


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