Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • ASCI Milestone Awards
    • Video Abstracts
    • Conversations with Giants in Medicine
  • Reviews
    • View all reviews ...
    • Clinical innovation and scientific progress in GLP-1 medicine (Nov 2025)
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • ASCI Milestone Awards
  • Video Abstracts
  • Conversations with Giants in Medicine
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
C-C chemokine–encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis
Sawsan Youssef, Gila Maor, Gizi Wildbaum, Nir Grabie, Alumit Gour-Lavie, Nathan Karin
Sawsan Youssef, Gila Maor, Gizi Wildbaum, Nir Grabie, Alumit Gour-Lavie, Nathan Karin
View: Text | PDF
Article

C-C chemokine–encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis

  • Text
  • PDF
Abstract

Depending on the method of immunization, a single administration of CFA may result in the development of a local inflammatory process or chronic polyadjuvant-induced arthritis (AA). We administered naked DNA vaccines encoding MIP-1α, MCP-1, MIP-1β, and RANTES to Lewis rats and confirmed that each of these vaccines induced immunological memory to the corresponding gene product. Upon induction of disease, this memory effectively inhibited the development of the autoimmune condition. Self-specific Ab’s developed in DNA-vaccinated animals were neutralizing in vitro and could adoptively transfer the beneficial effect of each vaccine. Repeated administration of the constructs encoding MCP-1, MIP-1α, or RANTES inhibited the development and progression of AA, even when each vaccine was administered only after the onset of disease. This suggests a highly effective way by which the immune system could be re-educated to generate protective immunity against its own harmful activities.

Authors

Sawsan Youssef, Gila Maor, Gizi Wildbaum, Nir Grabie, Alumit Gour-Lavie, Nathan Karin

×

Figure 6

Options: View larger image (or click on image) Download as PowerPoint
Anti-chemokine Ab’s produced by DNA vaccination block DTH response and p...
Anti-chemokine Ab’s produced by DNA vaccination block DTH response and provide subsequent protection from severe AA. (a) Eight groups of six rats each were immunized with CFA to develop poly-arthritis. Seven, 10, and 12 days after the active induction of disease, these rats were challenged (intravenously) with 200 μg of IgG (protein G purification, CNBr purification) from the different groups described in Figure 3. Control rats were injected with either PBS, IgG from naive rats, IgG from AA or from AA rats previously administered pcDNA3 alone. AA was scored daily by an observer blind to the experimental procedure. Results are shown as mean clinical score of six rats in each group ± SE. Five to 7 days after the last administration of neutralizing Ab’s to each of the above chemokines, disease severity regained the level of control AA rats (not shown). (b) Inhibition of adoptively induced DTH by anti–C-C chemokine Ab’s. Lewis rats were intravenously administered 107 activated CD4+ PPD-specific T cells and were randomly separated into eight groups of five rats each. One hour later each group was subjected to an in vivo administration (intravenously) of various Ab’s, as described above (a). Each rat was then immunized intradermally into the dorsal surface of the ear with 10 μg PPD in 25 μL of PBS (or with PBS alone). Results are presented as mean of delta ear thickness of five different ears ± SE.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts