title: Titrating T-cell epitopes within self-assembled vaccines optimizes CD4+ helper T cell and antibody outputs.
abstract: Epitope content plays a critical role in determining T-cell and antibody responses to vaccines, biomaterials, and protein therapeutics, but its effects are nonlinear and difficult to isolate. Here, molecular self-assembly is used to build a vaccine with precise control over epitope content, in order to finely tune the magnitude and phenotype of T helper and antibody responses. Self-adjuvanting peptide nanofibers are formed by co-assembling a high-affinity universal CD4+ T-cell epitope (PADRE) and a B-cell epitope from Staphylococcus aureus at specifiable concentrations. Increasing the PADRE concentration from micromolar to millimolar elicited bell-shaped dose-responses that are unique to different T-cell populations. Notably, the epitope ratios that maximize T follicular helper and antibody responses differed by an order of magnitude from those that maximized Th1 or Th2 responses. Thus, modular materials assembly provides a means of controlling epitope content and efficiently skewing the adaptive immune response in the absence of exogenous adjuvant; this approach may contribute to the development of improved vaccines and immunotherapies.
authors.affiliation: Department of Surgery, Committee of Immunology, University of Chicago, 5841 S. Maryland Avenue, MC5032, Chicago, IL, 60637, USA.
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Pompano
authors.forename: Jianjun
authors.initials: J
authors.lastname: Chen
authors.forename: Emily A
authors.initials: EA
authors.lastname: Verbus
authors.forename: Huifang
authors.initials: H
authors.lastname: Han
authors.forename: Arthur
authors.initials: A
authors.lastname: Fridman
authors.forename: Tessie
authors.initials: T
authors.lastname: McNeely
authors.forename: Joel H
authors.initials: JH
authors.lastname: Collier
authors.forename: Anita S
authors.initials: AS
authors.lastname: Chong
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D013211:Staphylococcus aureus / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014612:Vaccines / Q000276:immunology
chemical_list: D000906:Antibodies; D018984:Epitopes, T-Lymphocyte; D014612:Vaccines
keywords: MRSA; co-assembly; immunoengineering; scaffolds; self-adjuvanting