Modulating adaptive immune responses to peptide self-assemblies

Jai S. Rudra, Tao Sun, Katelyn C. Bird, Melvin D. Daniels, Joshua Z. Gasiorowski, Anita S. Chong, Joel H. Collier

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Self-assembling peptides and peptide derivatives have received significant interest for several biomedical applications, including tissue engineering, wound healing, cell delivery, drug delivery, and vaccines. This class of materials has exhibited significant variability in immunogenicity, with many peptides eliciting no detectable antibody responses but others eliciting very strong responses without any supplemental adjuvants. Presently, strategies for either avoiding strong antibody responses or specifically inducing them are not well-developed, even though they are critical for the use of these materials both within tissue engineering and within immunotherapies. Here, we investigated the molecular determinants and immunological mechanisms leading to the significant immunogenicity of the self-assembling peptide OVA-Q11, which has been shown previously to elicit strong antibody responses in mice. We show that these responses can last for at least a year. Using adoptive transfer experiments and T cell knockout models, we found that these strong antibody responses were T cell-dependent, suggesting a route for avoiding or ensuring immunogenicity. Indeed, by deleting amino acid regions in the peptide recognized by T cells, immunogenicity could be significantly diminished. Immunogenicity could also be attenuated by mutating key residues in the self-assembling domain, thus preventing fibrillization. A second self-assembling peptide, KFE8, was also nonimmunogenic, but nanofibers of OVA-KFE8 elicited strong antibody responses similar to OVA-Q11, indicating that the adjuvant action was not dependent on the specific self-assembling peptide sequence. These findings will facilitate the design of self-assembled peptide biomaterials, both for applications where immunogenicity is undesirable and where it is advantageous.

Original languageEnglish (US)
Pages (from-to)1557-1564
Number of pages8
JournalACS Nano
Volume6
Issue number2
DOIs
StatePublished - Feb 28 2012
Externally publishedYes

Fingerprint

Self assembly
Peptides
peptides
self assembly
assembling
antibodies
Antibodies
T-cells
tissue engineering
Tissue engineering
delivery
vaccines
wound healing
Vaccines
Biocompatible Materials
Nanofibers
Drug delivery
Biomaterials
determinants
mice

Keywords

  • biomaterial
  • scaffold
  • self-assembly
  • tissue engineering
  • vaccine

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)

Cite this

Rudra, J. S., Sun, T., Bird, K. C., Daniels, M. D., Gasiorowski, J. Z., Chong, A. S., & Collier, J. H. (2012). Modulating adaptive immune responses to peptide self-assemblies. ACS Nano, 6(2), 1557-1564. https://doi.org/10.1021/nn204530r

Modulating adaptive immune responses to peptide self-assemblies. / Rudra, Jai S.; Sun, Tao; Bird, Katelyn C.; Daniels, Melvin D.; Gasiorowski, Joshua Z.; Chong, Anita S.; Collier, Joel H.

In: ACS Nano, Vol. 6, No. 2, 28.02.2012, p. 1557-1564.

Research output: Contribution to journalArticle

Rudra, JS, Sun, T, Bird, KC, Daniels, MD, Gasiorowski, JZ, Chong, AS & Collier, JH 2012, 'Modulating adaptive immune responses to peptide self-assemblies', ACS Nano, vol. 6, no. 2, pp. 1557-1564. https://doi.org/10.1021/nn204530r
Rudra JS, Sun T, Bird KC, Daniels MD, Gasiorowski JZ, Chong AS et al. Modulating adaptive immune responses to peptide self-assemblies. ACS Nano. 2012 Feb 28;6(2):1557-1564. https://doi.org/10.1021/nn204530r
Rudra, Jai S. ; Sun, Tao ; Bird, Katelyn C. ; Daniels, Melvin D. ; Gasiorowski, Joshua Z. ; Chong, Anita S. ; Collier, Joel H. / Modulating adaptive immune responses to peptide self-assemblies. In: ACS Nano. 2012 ; Vol. 6, No. 2. pp. 1557-1564.
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