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

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 7

Options: View larger image (or click on image) Download as PowerPoint
Treatment of established AA by C-C chemokine DNA vaccine. (a) Lewis rats...
Treatment of established AA by C-C chemokine DNA vaccine. (a) Lewis rats were immunized with CFA to induce active AA and then randomly separated into three groups of 12 rats each. At the onset of disease (day 10) and on days 12 and 14 two of these groups were subjected to three repeated administrations of 300 μg per rat of either pcDNA3 alone or of the MCP-1 construct. The third group was inoculated with PBS. In a continuing experiment (b) the same protocol was applied on eight groups of 12 rats each treated with either pcDNA3 alone, RANTES, MCP-1, MIP-1α, MIP-1β, fractalkine, and soluble β-actin (cytoplasm form) constructs. The last group was inoculated with PBS. In both experiments AA was scored daily by an observer blind to the experimental procedure. Results are shown as mean clinical score of 12 rats ± SE. On day 24, rats (five per group) were evaluated for their ability to mount a PPD-specific DTH response (c), as described in Figure 6b. Data were determined as mean of five repeated measurements ± SE.