Chemically defined bacterial products with immunopotentiating activity.

The adjuvant activity of two chemically well-defined bacterial products is reviewed: (1) lipopolysaccharides of gram-negative bacillis and their acylated detoxified derivatives, and (2) mycobacterial water-soluble fractions and synthetic analogues. Water-soluble adjuvant can substitute for mycobacteria in Freund's adjuvant, but if it is administered in saline, it has little activity. In contrast, lipopolysaccharide under the same conditions markedly increases the humoral antibody response. However, the use of lipopolysaccharide is limited by its toxicity. Water-soluble adjuvant treated with phthalic or succinic anhydride was shown to be an adjuvant when administered in saline. Furthermore, synthetic M-acetyl-muramyl-L-alanyl-D-isoglutamine also increased the humoral immune response when given in aqueous medium instead of in the usual water-in-oil emulsion. This compound, which has a small molecular weight, is not mitogenic, immunogenic, or toxic in mice, and was shown to have adjuvant activity even when given by the oral route.