title: Assembly and Immunological Processing of Polyelectrolyte Multilayers Composed of Antigens and Adjuvants.
abstract: While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen-specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice.
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, 8228 Paint Branch Drive, Room 2212 Jeong H. Kim Building, College Park, Maryland 20742, United States.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Chiu
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, 8228 Paint Branch Drive, Room 2212 Jeong H. Kim Building, College Park, Maryland 20742, United States.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Gammon
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, 8228 Paint Branch Drive, Room 2212 Jeong H. Kim Building, College Park, Maryland 20742, United States.
authors.forename: James I
authors.initials: JI
authors.lastname: Andorko
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, 8228 Paint Branch Drive, Room 2212 Jeong H. Kim Building, College Park, Maryland 20742, United States.
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Tostanoski
authors.affiliation: Fischell Department of Bioengineering, University of Maryland , College Park, 8228 Paint Branch Drive, Room 2212 Jeong H. Kim Building, College Park, Maryland 20742, United States.|Department of Microbiology and Immunology, University of Maryland Medical School , 685 West Baltimore Street, HSF-I Suite 380, Baltimore, Maryland 21201, United States.|Marlene and Stewart Greenebaum Cancer Center , 22 S. Greene Street, Suite N9E17, Baltimore, Maryland 21201, United States.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Jewell
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000941:Antigens; D003713:Dendritic Cells; D051379:Mice; D000071228:Polyelectrolytes / Q000737:chemistry*; D014612:Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D000941:Antigens; D000071228:Polyelectrolytes; D014612:Vaccines
keywords: immunology; polyelectrolyte multilayer; rational design; self-assembly; vaccine