Biomaterials are receiving increased attention as vaccine adjuvants owing to their chemical and compositional definition and their ability to stimulate immune responses against a variety of co-delivered antigens.[1–6] Supramolecular self-assembly can be a useful route for producing such materials-based adjuvants,[1, 2, 4–9] but it has been largely restricted to the incorporation of short peptide epitopes rather than larger protein immunogens.[1, 4–8] In this report, we developed nanofibers displaying properly folded, biologically active protein antigens. Peptides bearing p-nitrophenyl phosphonate (pNP) ligands were self-assembled into nanofibers and subsequently reacted with cutinase fusion proteins via a covalent active site-directed capture approach to afford protein-laden nanofibers. These nanofibers could be formulated to present precisely controlled amounts of protein antigen and acted as selfadjuvanting vaccines in mice. Cutinase-pNP reactions were site-selective, allowing antigens to be conjugated without disrupting their tertiary structures, making the approach broadly useful for developing protein-bearing supramolecular materials in a range of applications including immunotherapies.

Adjuvants and delivery platforms that present properly folded protein antigens are important in the development of vaccines because they allow for broad immunogenicity in outbred populations compared with peptide vaccines, and because they can include conformational epitopes.[10] Supramolecular assemblies are gaining interest in this regard, because they can be functionalized with a high density of antigens, in some cases without perturbing antigen conformation or self-assembly of the material. For example, supramolecular nanoparticle vaccines have been designed to contain both folded protein antigens and peptide antigens that mimic native epitope conformations.[7, 8, 11–13] β-sheet-rich nanofibers of peptides and peptide amphiphiles can also act as self-adjuvanting vaccines,[1, 4, 6] and they have an