TNFalpha DNA vaccination prevents clinical manifestations of experimental antiphospholipid syndrome.
Naked DNA encoding TNFalpha was introduced to BALB/c mice with experimental antiphospholipid syndrome (APS) induced by beta2GPI. Administration of naked DNA encoding TNFalpha resulted in the generation of immunological memory to its gene product, associated with elevated circulating anti-TNFalpha antibodies. Enriched IgG fraction of the mouse anti-TNFalpha was biologically active since it prevented endothelial cell activation by TNFalpha e.g., inhibition of monocyte adhesion to activated endothelial cells (HUVEC). Mice immunized with beta2GPI, vaccinated with TNFalpha DNA at an early stage of disease development, showed decreased titres of circulating anti-beta2GPI antibodies as compared to the group of mice vaccinated with a control naked DNA. The reduction of antiphospholipid antibody production was followed by amelioration of the foetal loss, increased platelet count to normal values as well as normalization of the prolonged aPTT. APS mice which were introduced to the TNFalpha DNA vector at a later stage of the disease development, showed less improvement in their clinical manifestations. The current study suggests a way in which a DNA vaccine can be employed for induction of a protective immunity in experimental APS.
Blank
M
M
Center for Autoimmune diseases, Department of Medicine B, Sheba Medical Center, Tel-Hashomer, Israel.
Krause
I
I
Wildbaum
G
G
Karin
N
N
Shoenfeld
Y
Y
D000818:Animals; D000906:Antibodies / Q000097:blood; D016736:Antiphospholipid Syndrome / Q000209:etiology / Q000276:immunology* / Q000628:therapy*; D005260:Female; D006023:Glycoproteins / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*; D019444:Vaccines, DNA; D053482:beta 2-Glycoprotein I
D000906:Antibodies; D006023:Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D019444:Vaccines, DNA; D053482:beta 2-Glycoprotein I