The adjuvant properties of a nontoxic monophosphoryl lipid A in hyporesponsive and aging mice

The immunomodulatory action of a nontoxic monophosphoryl lipid A (MPL) and a toxic diphosphoryl lipid A (DPL) fraction derived from endotoxins of the heptoseless mutants of bacteria were studied. Both derivatives retained the ability characteristic of lipopolysaccharides, i.e., to enhance antibody formation in young adult mice when injected along with antigen and suppress antibody production when given 1 day before antigen. In aging mice, a model of immunodeficiency, a marked restoration of antibody formation was observed when antigen was injected together with either MPL or DPL. Levels of antibody in the aging mice became comparable with those observed in young adult mice. Moreover, both MPL and DPL enhanced antibody production significantly in the endotoxin low-responder mouse strains C3H/HeJ and C57Bl/10 ScN, whereas phenol-water-extracted endotoxin from an Rd mutant was ineffective. MPL and DPL also acted as suppressive agents when administered prior to antigen in the C3H/HeJ strain. Thus, the results from these studies show that the toxic properties of lipid A can be removed without eliminating immunomodulating activity and certain forms of lipid A can overcome the immunologic lesions of immunodeficient and hyporesponsive animals.