Monophosphoryl lipid A as an adjuvant. Past experiences and new directions

The current era of vaccinology has resulted in antigens produced by synthetic chemistry and by genetic engineering techniques; these may provide more effective and safe vaccines. Many of these antigens can be produced in large quantities and in relatively pure form. However, inherent in their simplified, defined structures is a lack of immunogenicity and they require an immunostimulant or adjuvant to elicit appropriate immunity. It has been the purpose of this chapter to document the potential use of MPL as a vaccine adjuvant. In this regard, it has been demonstrated that (1) MPL has retained the useful immunostimulating activities of the parent LPS molecule, but has greatly attenuated toxicity; (2) MPL produces diverse effects on the cellular elements of the immune system, including macrophage activation and T and B cell interaction, with concomitant cytokine and lymphokine release; (3) MPL has proven adjuvant activity, in both the cellular and humoral effector arms of immunity; (4) MPL has adjuvant activity when used alone, or in combination with other immunostimulants and delivery vehicles; and (5) MPL has been administered safely to humans in various clinical vaccine trials. Thus, MPL is emerging as a promising new adjuvant for use in human vaccines.