title: Impact of dose, route, and composition on the immunogenicity of immune polyelectrolyte multilayers delivered on gold templates.
abstract: Biomaterial vaccines offer new capabilities that can be exploited for both infectious disease and cancer. We recently developed a novel vaccine platform based on self-assembly of immune signals into immune polyelectrolyte multilayers (iPEMs). These iPEM vaccines are electrostatically assembled from peptide antigens and nucleic acid-based toll-like receptor agonists (TLRas) that serve as molecular adjuvants. Gold nanoparticles (AuNPs) coated with iPEMs stimulate effector cytokine secretion in vitro and expand antigen-specific T cells in mice. Here we investigated how the dose, injection route, and choice of molecular adjuvant impacts the ability of iPEMs to generate T cell immunity and anti-tumor response in mice. Three injection routes-intradermal, subcutaneous, and intramuscular-and three iPEM dosing levels were employed. Intradermal injection induced the most potent antigen-specific T cell responses and, for all routes, the level of response was dose-dependent. We further discovered that these vaccines generate durable memory, indicated by potent, antigen-specific CD8+T cell recall responses in mice challenged with vaccine 49 days after a prime-boost immunization regimen. In a common exogenous antigen melanoma model, iPEM vaccines slowed or stopped tumor growth more effectively than equivalent ad-mixed formulations. Further, iPEMs containing CpG-a TLR9a-were more potent compared with iPEMs containing polyIC, a TLR3a. These findings demonstrate the ability of iPEMs to enhance response to several different classes of vaccine cargos, supporting iPEMs as a simple vaccine platform that mimics attractive features of other nanoparticles using immune signals that can be self-assembled or coated on substrates. Biotechnol. Bioeng. 2017;114: 423-431. © 2016 Wiley Periodicals, Inc.
authors: Fischell Department of Bioengineering, University of Maryland, 2212 Jeong H. Kim Engineering Building, 8228 Paint Branch Drive, College Park, Maryland 20742.
authors: Peipei
authors: P
authors: Zhang
authors: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland.
authors: James I
authors: JI
authors: Andorko
authors: Fischell Department of Bioengineering, University of Maryland, 2212 Jeong H. Kim Engineering Building, 8228 Paint Branch Drive, College Park, Maryland 20742.|Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland.|Marlene and Stewart Greenebaum Cancer Center, Baltimore, Maryland.|United States Department of Veterans Affairs, Baltimore, Maryland.
authors: Christopher M
authors: CM
authors: Jewell
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D019496:Cancer Vaccines; D004333:Drug Administration Routes; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism; D000071228:Polyelectrolytes / Q000737:chemistry*; D014612:Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D000071228:Polyelectrolytes; D014612:Vaccines; D006046:Gold
keywords: adjuvant; cancer; immunology; nanotechnology; polyelectrolyte multilayer; vaccine