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
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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

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Self-specific Ab’s to the gene product of each DNA vaccine are continual...
Self-specific Ab’s to the gene product of each DNA vaccine are continually produced during the acute and the chronic phase of disease. Lewis rats were subjected to the administration of various C-C chemokine DNA constructs, as described in Figure 1. Control rats were injected with pcDNA3 alone or with PBS. Three weeks later these rats were administered CFA to induce poly-arthritis. At different time points the kinetics of anti-self Ab appearance in serum was determined by ELISA. Results are shown as mean of three different serum samples ± SE.