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The Enhancement of Antibody Formation by Escherichia Coli Lipopolysaccharide and Detoxified Derivatives

From the Department of Molecular Biology, Abbott Laboratories, North Chicago, Illinois 60064

Abstract

The formation of antibody to human serum albumin (HSA) in rats was greatly enhanced when the protein was linked covalently to E. coli lipopolysaccharide (LPS). The response was less when HSA and LPS were only mixed before injection and nil when they were injected at separate sites subcutaneously. In rats the adjuvant effect of coupling LPS to HSA was comparable to that of using Freund's adjuvant or alum precipitation. In rabbits Freund's adjuvant was significantly the more effective. By the use of two qualitatively different detoxified derivatives, an adjuvant effect approximately equal to that of LPS was obtained with 1000-fold less pyrogenicity. The data suggest that LPS enhances antibody formation by acting directly upon the cells which respond to antigen, and possibly at the antigen-sensitive sites. In this effect both the lipid and polysaceharide portions of LPS appear to play a role, with lipid being the more important.