Adjuvants for human vaccines

Abstract

Rational selection of individual adjuvants can often be made on the basis of innate molecular interactions of the foreign molecules with pattern recognition receptors such as Toll-like receptors. For example, monophosphoryl lipid A, a family of endotoxic TLR4 agonist molecules from bacteria, has recently been formulated with liposomes, oil emulsions, or aluminum salts for several vaccines. Combinations of antigens and adjuvants with particulate lipid or oil components may reveal unique properties of immune potency or efficacy, but these can sometimes be exhibited differently in rodents when compared to nonhuman primates or humans. New adjuvants, formulations, microinjection devices, and skin delivery techniques for transcutaneous immunization demonstrate that adjuvant systems can include combinations of strategies and delivery mechanisms for uniquely formulated antigens and adjuvants.

Figure 1

Schematic representation of O/W emulsion containing a TLR 4 Agonist (lipid A or derivatives). This type of adjuvant, referred to as MPL-SE (stable emulsion) or GLA-SE, has been used in vaccine trials against leishmaniasis, influenza, and other indications [6].

Figure 2

Strategies for transcutaneous immunization. Although TCI was enabled by the use of the antigen together with an adjuvant applied with an aqueous patch to unbroken skin, numerous alternative strategies and methods have been proposed and developed for using adjuvants, particles, microneedles, and other devices for achieving delivery of antigen through the stratum corneum. See [34, 42] for details.