ADJUVANT-FREE IN-VIVO TARGETING - ANTIGEN DELIVERY BY ALPHA(2)-MACROGLOBULIN ENHANCES ANTIBODY-FORMATION

The proteinase ''inhibitor'' alpha(2)-macroglobulin (alpha(2)M) is abl e to entrap and form covalent linkages with diverse proteins during a transient proteinase-activated state. These complexes are rapidly endo cytosed after binding to receptors present on macrophages and other ce lls. We have previously shown that compared to free hen egg lysozyme ( HEL), alpha(2)M-complexed HEL undergoes enhanced macrophage uptake, pr ocessing, and presentation to T hybridoma clones in vitro. Inasmuch as it is not clear whether T hybridoma responses accurately reflect prim ary immune responses in vivo, we studied antibody production in rabbit s using two Ag complexed with either human alpha(2)M (H alpha(2)M) or a homologous protein purified from rabbit plasma, alpha(1)-macroglobul in (R alpha(1)M). Pathogen-free NZW rabbits received s.c. injections w ith adjuvant-free preparations of free HEL or porcine pancreatic elast ase (PPE), H alpha(2)M-HEL-PPE complexes, R alpha(1)M-HEL-PPE complexe s, or mixtures of the uncomplexed proteins. Complexing the Ag to alpha (2)M resulted in 10 to 500-fold higher Ige titers compared to uncomple xed controls. Injection of Ag complexed to either H alpha(2)M or R alp ha(1)M resulted in levels of anti-HEL IgG comparable to those elicited by emulsification in CFA. Inasmuch as inflammatory proteinases such a s neutrophil elastase can initiate covalent complex formation with alp ha(2)M, we propose that ''proteinase-activated'' alpha(2)M may mediate receptor-enhanced Ag uptake by macrophages, resulting in augmented Ag processing and antibody production.