The adjuvant combination monophosphoryl lipid A and QS21 switches T cell responses induced with a soluble recombinant HIV protein from Th2 to Th1

The induction of protective immunity with; recombinant vaccines is dependen t on the identification of adjuvant or delivery systems that can augment im mune responses, especially cellular immune responses. to soluble protein an tigen. In this study we demonstrate that an adjuvant formulation comprising QS21, a purified form of saponin and 3(D)-monophosphoryl lipid A (MPL)I a nontoxic derivative of lipopolysaccharide (LPS), enhances cellular and humo ral immune responses to a recombinant HIV protein. Analysis of cytokine sec retion by antigen-specific T-cells from the spleen demonstrated that QS21 a ugmented Th1 and Th2 responses, whereas addition of 3(D)-MPL resulted in pr eferential induction of type 1 T-cells. Furthermore, analysis of the subcla ss of the IgG antibody in the serum in mice immunized with:ith gp120 with t he combined adjuvant formulation confirmed the selective activation of Th1 cells in vivo. 3(D)-MPL was found to enhance B7-1 expression and IL-12 prod uction by macrophages, a:which are known to be involved in the LPS-induced enhancement of Th1 responses. Thus 3(D)-MPL appears to act as an adjuvant, without the toxicity associated with LPS, by controlled and selective poten tiating effects on antigen presentation and T-cell activation. (C) 1999 Els evier Science Ltd. All rights reserved.