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    Characterization and optimization of the glucan particle-based vaccine platform

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    Clin._Vaccine_Immunol._2013_Hu ...
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    Authors
    Huang, Haibin
    Ostroff, Gary R.
    Lee, Chrono K.
    Specht, Charles A.
    Levitz, Stuart M.
    UMass Chan Affiliations
    Program in Molecular Medicine
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2013-10-01
    Keywords
    Animals
    CD4-Positive T-Lymphocytes
    Cytokines
    Drug Carriers
    Glucans
    Immunoglobulin G
    Mice
    Mice, Inbred C57BL
    Ovalbumin
    Saccharomyces cerevisiae
    Vaccination
    Vaccines
    Immunity
    Immunoprophylaxis and Therapy
    Medical Immunology
    Medicinal-Pharmaceutical Chemistry
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    Abstract
    Glucan particles (GPs) are hollow porous Saccharomyces cerevisiae cell walls that are treated so that they are composed primarily of beta-1,3-d-glucans. Our previous studies showed that GPs can serve as an effective vaccine platform. Here, we characterize CD4(+) T-cell and antibody responses in immunized mice as a function of antigen (ovalbumin) encapsulation, antigen dose, particle numbers, time, immunization schedule, and trapping methods. Although we found that GPs served as an effective adjuvant when admixed with free antigens for IgG1 antibody production, stronger CD4(+) T-cell and IgG2c antibody responses were stimulated when antigens were encapsulated inside GPs, suggesting that the GP platform acts as both an adjuvant and a delivery system. Vigorous T-cell and antibody responses were stimulated even at submicrogram antigen doses, as long as the number of GPs was kept at 5 x 10(7) particles per immunization. One prime and one boost were sufficient to elicit robust immune responses. In addition, strong antigen-specific antibody and T-cell responses prevailed up to 20 months following the last immunization, including those of gamma interferon (IFN-gamma), interleukin 17A (IL-17A), and dual IFN-gamma/IL-17A-secreting CD4(+) T cells. Finally, robust immune responses were observed using generally recognized as safe (GRAS) materials (alginate and calcium, with or without chitosan) to trap antigens within GPs. Thus, these studies demonstrate that antigens encapsulated into GPs make an effective vaccine platform that combines adjuvanticity and antigen delivery to elicit strong durable immune responses at relatively low antigen doses using translationally relevant formulations.
    Source
    Clin Vaccine Immunol. 2013 Oct;20(10):1585-91. doi: 10.1128/CVI.00463-13. Epub 2013 Aug 14. Link to article on publisher's site
    DOI
    10.1128/CVI.00463-13
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/30486
    PubMed ID
    23945157
    Related Resources
    Link to Article in PubMed
    Rights
    Copyright © 2013, American Society for Microbiology. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.
    ae974a485f413a2113503eed53cd6c53
    10.1128/CVI.00463-13
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