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.
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Acknowledgments
The authors gratefully acknowledge support from funds provided from the University of California, Berkeley and the University of Chicago, as well as research funding from the University of Chicago Institute for Translational Medicine (CTSA UL1 TR000430). We thank Dr. Eva Ulery for her comments and valuable discussion regarding the manuscript.
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Guest Editor: Aliasger Salem
Amanda Trent and Bret D. Ulery contributed equally to this work.
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Trent, A., Ulery, B.D., Black, M.J. et al. Peptide Amphiphile Micelles Self-Adjuvant Group A Streptococcal Vaccination. AAPS J 17, 380–388 (2015). https://doi.org/10.1208/s12248-014-9707-3
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DOI: https://doi.org/10.1208/s12248-014-9707-3