Enhancing the Magnitude of Antibody Responses through Biomaterial Stereochemistry

Abstract

D-Amino acid analogs of peptides and proteins are attractive for applications in biotechnology and medicine due to their reduced proteolytic sensitivity. Here, we report that self-assembling peptide nanofibers composed of D-amino acids act as immune adjuvants, and investigate their ability to induce antibody responses in comparison to their L-amino acid counterparts. The model antigenic peptide OVA (chicken egg ovalbumin aa 323−339) from chicken egg ovalbumin, known to elicit antibody responses in mice, was linked to an L-or Damino acid self-assembling peptide domain to generate enantiomeric nanofibers displaying the same epitope. The chiral nature of the fusion peptides was confirmed by circular dichrosim spectroscopy and transmission electron microscopy studies indicated that OVA-bearing enantiomers self-assembled into nanofibers with similar morphologies. In mice, D-amino acid peptide nanofibers displaying OVA elicited stronger antibody responses, equivalent levels of CD4+ T cell responses, and long-term antigen-presentation in vivo compared to L-amino acid nanofibers. Our findings indicate that self-assembling peptides composed of D-amino acids are strong immune adjuvants and that biomaterial stereochemistry can be used as a design tool to program adaptive immune responses for vaccine development.

Visible‐Light Microscopic Discovery of Up to 150 μm Long Helical Amyloid Fibrils Built of the Dodecapeptide H‐(Val‐Ala‐Leu)4‐OH and of Decapeptides Derived from Insulin

“… See also catalytically active amyloids and enantioselective self‐aggregation of peptides to form nanofibers . …”

Designing biomaterials with immunomodulatory properties for tissue engineering and regenerative medicine

“…Several studies have focused directly on the role of chemical functionality presented on surfaces to decipher how immue response is altered . For instance, peptides synthesized with either an L or D stereochemistry have been linked to a model antigen (ovalbumin, OVA) and used to vaccinate mice .…”

“…Several studies have focused directly on the role of chemical functionality presented on surfaces to decipher how immue response is altered . For instance, peptides synthesized with either an L or D stereochemistry have been linked to a model antigen (ovalbumin, OVA) and used to vaccinate mice . The D stereochemistry, which is less susceptible to enzymatic degradation, led to stronger antibody responses and prolonged antigen presentation compared to the L stereotype .…”

D-amino acid-containing supramolecular nanofibers for potential cancer therapeutics

“…A very recent work, by Yang et al, showed that D-peptide based nanofibers/hydrogel serve as the carrier of antigens for cancer therapy [118], further demonstrating the potentials of this molecular platform based on D-peptides. Considering the advantages of D-peptides, it is likely that future exploration will lead to more applications of D-peptides [119]. …”