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Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization.

Publication ,  Journal Article
Kelly, SH; Cossette, BJ; Varadhan, AK; Wu, Y; Collier, JH
Published in: ACS biomaterials science & engineering
May 2021

Effective sublingual peptide immunization requires overcoming challenges of both delivery and immunogenicity. Mucosal adjuvants, such as cyclic-dinucleotides (CDN), can promote sublingual immune responses but must be codelivered with the antigen to the epithelium for maximum effect. We designed peptide-polymer nanofibers (PEG-Q11) displaying nona-arginine (R9) at a high density to promote complexation with CDNs via bidentate hydrogen-bonding with arginine side chains. We coassembled PEG-Q11 and PEG-Q11R9 peptides to titrate the concentration of R9 within nanofibers. In vitro, PEG-Q11R9 fibers and cyclic-di-GMP or cyclic-di-AMP adjuvants had a synergistic effect on enhancing dendritic cell activation that was STING-dependent and increased monotonically with increasing R9 concentration. The polyvalent display of R9 on assembled nanofibers was significantly more effective at promoting CDN-mediated DC activation in vitro than mixing nanofibers with an equimolar concentration of unassembled R9 peptide. The sublingual administration of nanofibers revealed a bell-shaped trend between increasing R9 concentration and enhancements to antigen trafficking and the activation of DCs in the draining lymph nodes. Intermediate levels of R9 within sublingually administered PEG-Q11 fibers were optimal for immunization, suggesting a balance between polyarginine's ability to sequester CDNs along the nanofiber and its potentially detrimental mucoadhesive interactions. These findings present a potentially generalizable biomaterial strategy for enhancing the potency of CDN adjuvants and reveal important design considerations for the nascent field of sublingual biomaterial immunization.

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Published In

ACS biomaterials science & engineering

DOI

EISSN

2373-9878

ISSN

2373-9878

Publication Date

May 2021

Volume

7

Issue

5

Start / End Page

1876 / 1888

Related Subject Headings

  • Peptides
  • Nanofibers
  • Immunization
  • Administration, Sublingual
  • 4003 Biomedical engineering
  • 0903 Biomedical Engineering
 

Citation

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Kelly, S. H., Cossette, B. J., Varadhan, A. K., Wu, Y., & Collier, J. H. (2021). Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization. ACS Biomaterials Science & Engineering, 7(5), 1876–1888. https://doi.org/10.1021/acsbiomaterials.0c01429
Kelly, Sean H., Benjamin J. Cossette, Ajay K. Varadhan, Yaoying Wu, and Joel H. Collier. “Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization.ACS Biomaterials Science & Engineering 7, no. 5 (May 2021): 1876–88. https://doi.org/10.1021/acsbiomaterials.0c01429.
Kelly SH, Cossette BJ, Varadhan AK, Wu Y, Collier JH. Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization. ACS biomaterials science & engineering. 2021 May;7(5):1876–88.
Kelly, Sean H., et al. “Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization.ACS Biomaterials Science & Engineering, vol. 7, no. 5, May 2021, pp. 1876–88. Epmc, doi:10.1021/acsbiomaterials.0c01429.
Kelly SH, Cossette BJ, Varadhan AK, Wu Y, Collier JH. Titrating Polyarginine into Nanofibers Enhances Cyclic-Dinucleotide Adjuvanticity in Vitro and after Sublingual Immunization. ACS biomaterials science & engineering. 2021 May;7(5):1876–1888.
Journal cover image

Published In

ACS biomaterials science & engineering

DOI

EISSN

2373-9878

ISSN

2373-9878

Publication Date

May 2021

Volume

7

Issue

5

Start / End Page

1876 / 1888

Related Subject Headings

  • Peptides
  • Nanofibers
  • Immunization
  • Administration, Sublingual
  • 4003 Biomedical engineering
  • 0903 Biomedical Engineering