C-C chemokine-encoding DNA vaccines enhance breakdown of tolerance to their gene products and treat ongoing adjuvant arthritis.
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-1 alpha, MCP-1, MIP-1 beta, 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-1 alpha, 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.
Department of Immunology, Technion, Haifa, Israel.
S
S
Youssef
G
G
Maor
G
G
Wildbaum
N
N
Grabie
A
A
Gour-Lavie
N
N
Karin
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity; D018932:Chemokine CCL2 / Q000235:genetics; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics; D019742:Chemokines, CC / Q000235:genetics*; D005260:Female; D007108:Immune Tolerance / Q000235:genetics*; D007114:Immunization; D007156:Immunologic Memory; D019402:Macrophage Inflammatory Proteins / Q000235:genetics; D009500:Neutralization Tests; D051381:Rats; D011917:Rats, Inbred Lew; D017634:Self Tolerance / Q000235:genetics; D019444:Vaccines, DNA / Q000494:pharmacology*
D001323:Autoantibodies; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D019444:Vaccines, DNA