The development of immunotherapies has resulted in a dramatic decrease in the number of cases of several diseases, including measles and polio, demonstrating the need to continue vaccine research to eliminate prevalent diseases, such as malaria and ebola. Some of the most successful vaccines have been empirically determined, leaving the mode of action unknown. Consequently, vaccine development can be slow and the available formulations are not as effective as they should be. We are working on understanding how the immune system functions and battles pathogens on a fundamental level in order to design more successful and safer vaccines. Recently, the use of multiple immune agonists, especially Toll-like receptor (TLR) agonists, has been used to enhance specific immune responses. Thus, indicating that multiple agonists will be needed, instead of one agonist, to design vaccines that can eliminate promiscuous diseases. Using synthetic chemistry, we have probed immune system responses by conjugating multiple TLR agonists together. Incubating our constructs with immune cells, we have shown modulation of innate immune responses, suggesting downstream changes in adaptive immune activation. Here, we are applying our multi-agonist compounds to antigen presentation <i>via </i>conjugation to a peptide antigen. Consequently, we can determine how different combinations of agonists affect antigen presentation and subsequently T cell and antibody responses. Ultimately, these multi-agonist scaffolds can mechanistically inform us about immune system signaling and activation, allowing us to design more effective vaccines.

Application of multi-agonist scaffolds to modulate antigen presentation and adaptive immunity

249th National Meeting (2015)

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