A comparison of the immunomodulating properties of two forms of monophosphory1 lipid A analogues

This investigation compared the immunomodulating activities of two forms of monophosphoryl lipid A, which are analogues of bacterial lipopolysaccharides with little or no toxicity. Tested were a synthetic compound designated 504 and a purified compound, isolated from bacterial cell walls designated MPL. Both of these clinical adjuvant candidates were effective in mice in exerting strong immunomodulating activity in the following areas: (a) enhancing antibody production in young and aging mice; (b) suppressing antibody formation under different experimental conditions; (c) activating macrophages to secrete interleukin 1, hydrogen peroxide, and superoxide anion; and (d) stimulating proliferation of spleen cells from C3H/HeN mice. Both exhibited considerably reduced toxicity in LD₅₀ assays when compared to native lipopolysaccharides (LPS). The LD₅₀ for MPL was 225 times and that of compound 504, 40 times that of native LPS in the exquisitely sensitive, galactosamine-loaded C57BL/6 murine strain.