Switching the Immunogenicity of Peptide Assemblies Using Surface Properties

Biomaterials created from supramolecular peptides, proteins, and their derivatives have been receiving increasing interest for both immunological applications, such as vaccines and immunotherapies, as well as ostensibly nonimmunological applications, such as therapeutic delivery or tissue engineering. However, simple rules for either maximizing immunogenicity or abolishing it have yet to be elucidated, even though immunogenicity is a prime consideration for the design of any supramolecular biomaterial intended for use in vivo. Here, we investigated a range of physicochemical properties of fibrillized peptide biomaterials, identifying negative surface charge as a means for completely abolishing antibody and T cell responses against them in mice, even when they display a competent epitope. The work was facilitated by the modularity of the materials, which enabled the generation of a set of co-assembled fibrillar peptide materials with broad ranges of surface properties. It was found that negative surface charge, provided via negatively charged amino acid residues, prevented T cell and antibody responses to antigen-carrying assemblies because it prevented uptake of the materials by antigen-presenting cells (APCs), which in turn prevented presentation of the epitope peptide in the APCs’ major histocompatibility class II molecules. Conversely, positive surface charge augmented the uptake of fibrillized peptides by APCs. These findings suggest that some surface characteristics, such as extensive negative charge, should be avoided in vaccine design using supramolecular peptide assemblies. More importantly, it provides a strategy to switch off potentially problematic immunogenicity for using these materials in nonimmunological applications.