Synthetic iNKT cell-agonists as vaccine adjuvants--finding the balance

The unique position of invariant natural killer T (iNKT) cells at the interface of the innate and adaptive arms of the immune response, combined with their ability to modulate the activity of antigen-presenting cells, has led to their intensive investigation as a means of augmenting the immune response both in vaccination strategies for microbial infections and in tumor immunotherapy. Several synthetic iNKT-cell agonists that have potential as vaccine adjuvants have been identified, but these are not without their limitations-strong agonists can lead to the undesirable effects associated with overstimulation of the immune system, whereas too weak agonists may provide insufficient iNKT cell help to stimulate maturation of dendritic cells and differentiation of B cells. In this article we explore strategies being investigated as means of increasing the specificity of and controlling the magnitude of the immune response generated by activation of iNKT cells with synthetic agonists.