Safety Evaluation of Monophosphoryl Lipid A (MPL): An Immunostimulatory Adjuvant

Animal models have shown the potential use of monophosphoryl lipid A (MPL®), a detoxified bacterial lipopolysaccharide, as a vaccine adjuvant. Immunostimulatory activity with diverse effects on the cellular elements of the immune system has been demonstrated and a range of vaccines incorporating MPL, including allergy vaccines, are currently under clinical evaluation. A series of preclinical safety investigations was performed to support clinical use of MPL as used in allergy vaccines and comprised cardiovascular/respiratory assessment in dog (up to 100 μg/kg/day); repeat-dose toxicity in rat, rabbit, and dog (up to 2500 and 1200 μg/kg/day in the rat and dog, respectively); reproduction toxicity in rat and rabbit (up to 100 μg/kg/day); and genotoxicity studies. Overall, repeat-dose toxicity studies in the rat and dog showed expected immunostimulatory effects and/or signs of toxicity associated with overstimulation of the immune system (notably increased spleen weight and white blood cell values). Studies in the rabbit with weekly doses of MPL produced no effects. MPL was shown to have no adverse effects on cardiovascular/respiratory function, reproduction, and genotoxicity.