Modular control of innate immune signaling using self-assembly of immune signals

Conference Dates

June 5-9, 2018


Vaccines play an increasingly important role in preventing and treating diseases ranging from infectious pathogens to cancer because these technologies harness the specificity of the immune system to clear disease without targeting the body’s own cells. To realize these goals, new understanding of adjuvants – molecules added to vaccines to enhance function – is needed to support design of next-generation vaccines that elicit responses tailored for specific diseases. We recently reported a simple nanotechnology platform based on self-assembly of peptide antigen and a molecular toll-like receptor agonist (TLRa) to create modular vaccine designs (ACS Nano 2016, ACS Nano 2015). These structures – termed immune polyelectrolyte multilayers (iPEMs) – juxtapose antigen and TLRa at high densities, and offer 100% cargo loading since no carrier component is needed. This modularity also creates the possibility of rationally designing iPEMs that trigger multiple immune pathways with distinct control over the relative activation levels. In cancer, for example, activating multiple innate pathways has been linked to improved patient outcomes in human clinical trials. To exploit iPEMs in this manner, we designed iPEM architectures incorporating a conserved human cancer antigen (Trp2), and a range of molecularly-defined TLRa that spanned different TLRa classes and species (i.e., mouse and human): agonists for TLR3, TLR9, and TLR13. iPEMs were assembled from Trp2 and one, two, or three TLRas, or alternatively, using two different TLRas at varying compositions. To form carrier free capsules using these design schemes, Trp2 was appended with cationic amino acids, then adsorbed onto a sacrificial colloidal template, with alternating adsorption steps employing the specified TLRas (anionic).

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