Vaccines are a powerful tool of modern medicine as they have prevented millions of deaths and countless illnesses. Although empirical vaccine development has been successful to address many diseases, it has failed to combat others, like HIV and malaria, demonstrating the need for more effective, rationally designed vaccines. We are working to better understand the process of immune system stimulation in order to design more effective vaccines. Successful vaccines elicit potent immune responses by activating pattern recognition receptors, including Toll-like receptors (TLRs). We are developing novel immunostimulants by covalently linking synergistic combinations of TLR agonists which can elicit a directed immune response to desired antigens. Recently, we have shown that a covalently linked tri-agonist (TLR 4, 7, and 9 agonists) elicits a distinctive immune response and enhances the antibody response toward vaccinia virus in a vaccination model. Here, we are synthesizing new TLR tri-agonist combinations and evaluating their immune activity. By understanding how different tri-agonist combinations result in distinct response profiles, we can design optimal immune responses toward desired antigens to develop more effective vaccines.

Directed immune responses via covalently-linked TLR agonist combinations

251st National Meeting (2016)

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