Peptide-based supramolecular vaccine systems.

Currently approved replication-competent and inactivated vaccines are limited by excessive reactogenicity and poor safety profiles, while subunit vaccines are often insufficiently immunogenic without co-administering exogenous adjuvants. Self-assembling peptide-, peptidomimetic-, and protein-based biomaterials offer a means to overcome these challenges through their inherent modularity, multivalency, and biocompatibility. As these scaffolds are biologically derived and present antigenic arrays reminiscent of natural viruses, they are prone to immune recognition and are uniquely capable of functioning as self-adjuvanting vaccine delivery vehicles that improve humoral and cellular responses. Beyond this intrinsic immunological advantage, the wide range of available amino acids allows for facile de novo design or straightforward modifications to existing sequences. This has permitted the development of vaccines and immunotherapies tailored to specific disease models, as well as generalizable platforms that have been successfully applied to prevent or treat numerous infectious and non-infectious diseases. In this review, we briefly introduce the immune system, discuss the structural determinants of coiled coils, ß-sheets, peptide amphiphiles, and protein subunit nanoparticles, and highlight the utility of these materials using notable examples of their innate and adaptive immunomodulatory capacity. STATEMENT OF SIGNIFICANCE: Subunit vaccines have recently gained considerable attention due to their favorable safety profiles relative to traditional whole-cell vaccines; however, their reduced efficacy requires co-administration of reactogenic adjuvants to boost immune responses. This has led to collaborative efforts between engineers and immunologists to develop nanomaterial-based vaccination platforms that can elicit protection without deleterious side effects. Self-assembling peptidic biomaterials are a particularly attractive approach to this problem, as their structure and function can be controlled through primary sequence design and their capacity for multivalent presentation of antigens grants them intrinsic self-adjuvanticity. This review introduces the various architectures adopted by self-assembling peptides and discusses their application as modulators of innate and adaptive immunity.

Self-Assembly of Block Heterochiral Peptides into Helical Tapes.

Patterned substitution of d-amino acids into the primary sequences of self-assembling peptides influences molecular-level packing and supramolecular morphology. We report that block heterochiral analogs of the model amphipathic peptide KFE8 (Ac-FKFEFKFE-NH2), composed of two FKFE repeat motifs with opposite chirality, assemble into helical tapes with dimensions greatly exceeding those of their fibrillar homochiral counterparts. At sufficient concentrations, these tapes form hydrogels with reduced storage moduli but retain the shear-thinning behavior and consistent mechanical recovery of the homochiral analogs. Varying the identity of charged residues (FRFEFRFE and FRFDFRFD) produced similarly sized nonhelical tapes, while a peptide with nonenantiomeric l- and d-blocks (FKFEFRFD) formed helical tapes closely resembling those of the heterochiral KFE8 analogs. A proposed energy-minimized model suggests that a kink at the interface between l- and d-blocks leads to the assembly of flat monolayers with nonidentical surfaces that display alternating stacks of hydrophobic and charged groups.