title: A self-assembling peptide acting as an immune adjuvant.
abstract: The development of vaccines and other immunotherapies has been complicated by heterogeneous antigen display and the use of incompletely defined immune adjuvants with complex mechanisms of action. We have observed strong antibody responses in mice without the coadministration of any additional adjuvant by noncovalently assembling a T and B cell epitope peptide into nanofibers using a short C-terminal peptide extension. Self-assembling peptides have been explored recently as scaffolds for tissue engineering and regenerative medicine, but our results indicate that these materials may also be useful as chemically defined adjuvants. In physiological conditions, these peptides self-assembled into long, unbranched fibrils that displayed the epitope on their surfaces. IgG1, IgG2a, and IgG3 were raised against epitope-bearing fibrils in levels similar to the epitope peptide delivered in complete Freund's adjuvant (CFA), and IgM production was even greater for the self-assembled epitope. This response was dependent on self-assembly, and the self-assembling sequence was not immunogenic by itself, even when delivered in CFA. Undetectable levels of interferon-gamma, IL-2, and IL-4 in cultures of peptide-challenged splenocytes from immunized mice suggested that the antibody responses did not involve significant T cell help.
authors.affiliation: Department of Surgery and Committee on Molecular Medicine, University of Chicago, 5841 S Maryland Avenue, Chicago, IL 60637, USA.
authors.forename: Jai S
authors.initials: JS
authors.lastname: Rudra
authors.forename: Ye F
authors.initials: YF
authors.lastname: Tian
authors.forename: Jangwook P
authors.initials: JP
authors.lastname: Jung
authors.forename: Joel H
authors.initials: JH
authors.lastname: Collier
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005620:Freund's Adjuvant / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D057139:Nanofibers; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D011487:Protein Conformation; D013601:T-Lymphocytes / Q000276:immunology; D023822:Tissue Engineering / Q000379:methods
chemical_list: D000276:Adjuvants, Immunologic; D000939:Epitopes; D007074:Immunoglobulin G; D010446:Peptide Fragments; D010047:Ovalbumin; D005620:Freund's Adjuvant