Any successful immunologic therapy must not only raise the proper strength of an immune response, but it must also raise the correct phenotype, which can be challenging owing to the complexity of the immune system. Here we will describe self-adjuvanting, modular, supramolecuar materials capable of tuning immune phenotype using two models: a vaccine against methicillin-resistant <i>S. aureus </i>(MRSA), and an immunotherapy for chronic inflammatory diseases. In both, fibrillizing peptides containing variable B cell and T cell epitopes were designed to co-assemble into nanofibers. In the MRSA vaccine, we found that the ratio between the B cell epitope and the T cell epitope significantly modulated both the strength and the phenotype of the response, with different T cell subsets being favored at different compositions. Only epitope ratios corresponding to the maximal Tfh cell and antibody responses improved the healing of MRSA skin lesions, illustrating the need to target such ratios precisely. Towards treating chronic inflammatory diseases, we employed a B cell epitope from TNF-alpha and an exogenous T cell epitope. In this model, we found that TNF-reactive antibodies could be raised in mice without T cell responses to the TNF epitope, allowing the accumulation of TNF-neutralizing antibodies in the serum. In both systems, the ability to adjust the strength and phenotype of the immune response was facilitated by the materials’ modular design.

Supramolecular peptide immunomodulators

249th National Meeting (2015)

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