Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination

Amanda Trent, Bret D. Ulery, Matthew J. Black, John C. Barrett, Simon Liang, Yulia Kostenko, Natalie A. David, Matthew V. Tirrell

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Delivery system design and adjuvant development are crucially important areas of research for improving vaccines. Peptide amphiphile micelles are a class of biomaterials that have the unique potential to function as both vaccine delivery vehicles and self-adjuvants. In this study, peptide amphiphiles comprised of a group A streptococcus B cell antigen (J8) and a dialkyl hydrophobic moiety (diC16) were synthesized and organized into self-assembled micelles, driven by hydrophobic interactions among the alkyl tails. J8-diC16 formed cylindrical micelles with highly α-helical peptide presented on their surfaces. Both the micelle length and secondary structure were shown to be enhanced by annealing. When injected into mice, J8-diC16 micelles induced a strong IgG1 antibody response that was comparable to soluble J8 peptide supplemented with two classical adjuvants. It was discovered that micelle adjuvanticity requires the antigen be a part of the micelle since separation of J8 and the micelle was insufficient to induce an immune response. Additionally, the diC16 tail appears to be non-immunogenic since it does not stimulate a pathogen recognition receptor whose agonist (Pam3Cys) possesses a very similar chemical structure. The research presented in this paper demonstrates the promise peptide amphiphile micelles have in improving the field of vaccine engineering.

Original languageEnglish (US)
Pages (from-to)380-388
Number of pages9
JournalAAPS Journal
Volume17
Issue number2
DOIs
StatePublished - Mar 1 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2014, American Association of Pharmaceutical Scientists.

Keywords

  • J8 peptide
  • group A streptococcus
  • peptide amphiphile micelles
  • self-adjuvant
  • vaccine

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