title: Peptide amphiphile micelles self-adjuvant group A streptococcal vaccination.
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.
authors.affiliation: Biomolecular Science and Engineering Program, University of California, Santa Barbara, California, 93106, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Trent
authors.forename: Bret D
authors.initials: BD
authors.lastname: Ulery
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Black
authors.forename: John C
authors.initials: JC
authors.lastname: Barrett
authors.forename: Simon
authors.initials: S
authors.lastname: Liang
authors.forename: Yulia
authors.initials: Y
authors.lastname: Kostenko
authors.forename: Natalie A
authors.initials: NA
authors.lastname: David
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Tirrell
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D010455:Peptides / Q000737:chemistry*; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000302:isolation & purification
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D007074:Immunoglobulin G; D008823:Micelles; D010455:Peptides; D022541:Streptococcal Vaccines