Enhancing the Magnitude of Antibody Responses through Biomaterial Stereochemistry

Rajagopal Appavu, Charles B. Chesson, Alexey Y. Koyfman, Joshua D. Snook, Frederick J. Kohlhapp, Andrew Zloza, Jai S. Rudra

Research output: Contribution to journalArticle

16 Scopus citations

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 d-amino 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.

Original languageEnglish (US)
Pages (from-to)601-609
Number of pages9
JournalACS Biomaterial Science and Engineering
Volume1
Issue number7
DOIs
StatePublished - Dec 14 2015

Keywords

  • adjuvant
  • enantiomer
  • nanofiber
  • peptide
  • self-assembly
  • stereochemistry

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering

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  • Cite this

    Appavu, R., Chesson, C. B., Koyfman, A. Y., Snook, J. D., Kohlhapp, F. J., Zloza, A., & Rudra, J. S. (2015). Enhancing the Magnitude of Antibody Responses through Biomaterial Stereochemistry. ACS Biomaterial Science and Engineering, 1(7), 601-609. https://doi.org/10.1021/acsbiomaterials.5b00139