Mode of Action of Adjuvants: Retinol and other Lysosome-Labilizing Agents As Adjuvants

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Abstract
Several agents known to labilize lysosomal membranes were found to have adjuvant effects, increasing the antibody response in mice immunized with bovine serum albumin (BSA). Two agents were particularly effective: retinol (vitamin A alcohol) and E. coli lipopolysaccharide (LPS). Although the highest antibody levels were observed in mice given retinol in incomplete Freund's adjuvant, smaller amounts of LPS were needed to obtain an adjuvant effect. When free BSA was administered alone, antibody levels were low but rose with increasing doses of antigen. Increasing the concentration of adjuvant raised antibody levels to a plateau level. In mice treated with adjuvants, increasing doses of antigen depressed antibody responses. There seems to be a relationship between the capacity of different agents to labilize lysosomal membranes and their potency as adjuvants. The response to BSA can be considered as the end result of two processes, immunization and tolerance-induction. The latter is favored by free antigen, whereas immunization is favored by presenting BSA in particulate form or together with adjuvants.

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