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    Impact of dose, route, and composition on the immunogenicity of immune polyelectrolyte multilayers delivered on gold templates

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    Author
    Zhang, P.
    Andorko, J.I.
    Jewell, C.M.
    Date
    2017
    Journal
    Biotechnology and Bioengineering
    Publisher
    John Wiley and Sons Inc.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://www.doi.org/10.1002/bit.26083
    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. Copyright 2016 Wiley Periodicals, Inc.
    Keyword
    adjuvant
    cancer
    immunology
    nanotechnology
    polyelectrolyte multilayer
    vaccine
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85006742115&doi=10.1002%2fbit.26083&partnerID=40&md5=1dfb3404bec6252e6995014920942589; http://hdl.handle.net/10713/9919
    ae974a485f413a2113503eed53cd6c53
    10.1002/bit.26083
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