Mechanisms of action of nonionic block copolymer adjuvants.

Nonionic block copolymer adjuvants typically induce high-titer, long-lasting antibody responses, cell-mediated immunity, CTLs, and modulate the isotype and specificity of antibody. Their primary activity is modulation of hydrophobic adhesive interactions. The copolymers adhere to lipids, promote retention of protein antigen to surfaces, activate complement, and induce expression of class II (IA) on macrophages. They produce a concentrated surface matrix of antigen and activated host mediators that facilitates antigen presentation to cells of the immune system. The copolymer adjuvants act synergistically with multiple MDP and LPS preparations to increase total titers, especially those of the IgG2a and IgG2b isotypes. A surprising discovery was that they influence the specificity of antibody by at least two mechanisms. Saline formulations and oil-in-water (o/w) emulsions induced more antibody against labile, conformationally dependent epitopes on the surface of particles than water-in-oil (w/o) emulsions. Finally, we found that very large copolymers are able to stabilize water-in-oil-in-water (w/o/w) or multiple emulsions that can protect antigen during passage through the upper GI tract. They are therefore attractive vehicles for oral delivery of vaccines.