Covalently coupled immunostimulant heterodimers

Abstract

We report increased stimulation of dendritic cells via heterodimers of immunostimulants formed at a discrete molecular distance. Many vaccines present spatially organized agonists to immune cell receptors. These receptors cluster suggesting that signaling is increased by spatial organization and receptor proximity, but this has not been directly tested for multiple, unique receptors. In this study we probe the spatial aspect of immune cell activation using heterodimers of two covalently attached immunostimulants. Big PAMPin': Many vaccines present spatially organized agonists known as pathogen-associated molecular patterns (PAMPs) to immune-cell receptors (see picture, left). In a study to probe the spatial aspects of immune-cell activation involving multiple, unique receptors, greater stimulation of dendritic cells was observed with heterodimers of covalently linked immunostimulants than with a mixture of the two unconjugated immunostimulants. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.