TNF αDNA vaccination prevents clinical manifestations of experimental antiphospholipid syndrome

Abstract

Naked DNA encoding TNFa was introduced to BALB/c mice with experimental antiphospholipid syndrome (APS) induced by b2GPI. Administration of naked DNA encoding TNFa resulted in the generation of immunological memory to its gene product, associated with elevated circulating anti-TNFa antibodies. Enriched IgG fraction of the mouse anti-TNFa was biologically active since it prevented endothelial cell activation by TNFa, e.g., inhibition of monocyte adhesion to activated endothelial cells (HUVEC). Mice immunized with b2GPI, vaccinated with TNFa DNA at an early stage of disease development, showed decreased titres of circulating anti-b2GPI antibodies as compared to the group of mice vaccinated with a control naked DNA. The reduction of anti-phospholipid 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 TNFa 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.