STRUCTURALLY WELL-DEFINED MACROPHAGE ACTIVATING FACTOR DERIVED FROM VITAMIN-D-3-BINDING PROTEIN HAS A POTENT ADJUVANT ACTIVITY FOR IMMUNIZATION

Freund's adjuvant produced severe inflammation that augments developme nt of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Si nce macrophage activation for phagocytosis and antigen processing is t he first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrop hage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrop hage activating cascade that requires participation of serum vitamin D -3-binding protein (DBP; human DBP is known as (jc protein) and glycos idases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF: we have e ver encountered. Administration of GcMAF (20 or 100pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and a ctivation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 da ys. Thus, GcMAF has a potent adjuvant activity for immunization. Altho ugh malignant tumours are poorly immunogenic, 4 days after GcMAF-prime d immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.