Comparative study of α-helical and β-sheet self-assembled peptide nanofiber vaccine platforms: influence of integrated T-cell epitopes.

Journal Article (Journal Article)

Several different self-assembling peptide systems that form nanofibers have been investigated as vaccine platforms, but design principles for adjusting the character of the immune responses they raise have yet to be well articulated. Here we compared the immune responses raised by two structurally dissimilar peptide nanofibers, one a β-sheet fibrillar system (Q11), and one an α-helical nanofiber system (Coil29), hypothesizing that integrated T-cell epitopes within the latter would promote T follicular helper (Tfh) cell engagement and lead to improved antibody titers and quality. Despite significantly different internal structures, nanofibers of the two peptides exhibited surprisingly similar nanoscale morphologies, and both were capable of raising strong antibody responses to conjugated peptide epitopes in mice without adjuvant. Both were minimally inflammatory, but as hypothesized Coil29 nanofibers elicited antibody responses with higher titers and avidities against a conjugated model epitope (OVA323-339) and a candidate peptide epitope for vaccination against S. aureus. Subsequent investigation indicated that Coil29 nanofibers possessed internal CD4+ T cell epitopes: whereas Q11 nanofibers required co-assembly of additional CD4+ T cell epitopes to be immunogenic, Coil29 nanofibers did not. Coil29 nanofibers also raised stronger germinal center B cell responses and follicular helper T cell (Tfh) responses relative to Q11 nanofibers, likely facilitating the improvement of the antibody response. These findings illustrate design strategies for improving humoral responses raised by self-assembled peptide nanofibers.

Full Text

Duke Authors

Cited Authors

  • Wu, Y; Kelly, SH; Sanchez-Perez, L; Sampson, JH; Collier, JH

Published Date

  • June 21, 2020

Published In

Volume / Issue

  • 8 / 12

Start / End Page

  • 3522 - 3535

PubMed ID

  • 32452474

Pubmed Central ID

  • PMC7665831

Electronic International Standard Serial Number (EISSN)

  • 2047-4849

Digital Object Identifier (DOI)

  • 10.1039/d0bm00521e

Language

  • eng

Conference Location

  • England