Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine
beta-Glucans; Saccharomyces cerevisiae; Dendritic Cells; Ovalbumin; Immunity, Cellular; CD4-Positive T-Lymphocytes
Immunology and Infectious Disease
beta-Glucan particles (GPs) are purified Saccharomyces cerevisiae cell walls treated so that they are primarily beta1,3-d-glucans and free of mannans and proteins. GPs are phagocytosed by dendritic cells (DCs) via the Dectin-1 receptor, and this interaction stimulates proinflammatory cytokine secretion by DCs. As the hollow, porous GP structure allows for high antigen loading, we hypothesized that antigen-loaded GPs could be exploited as a receptor-targeted vaccine delivery system. Ovalbumin (OVA) was electrostatically complexed inside the hollow GP shells (GP-OVA). Incubation of C57BL/6J mouse bone marrow-derived DCs with GP-OVA resulted in phagocytosis, upregulation of maturation markers, and rapid proteolysis of OVA. Compared with free OVA, GP-OVA was >100-fold more potent at stimulating the proliferation of OVA-reactive transgenic CD8(+) OT-I and CD4(+) OT-II T cells, as measured by in vitro [(3)H]thymidine incorporation using DCs as antigen-presenting cells. Next, immune responses in C57BL/6J mice following subcutaneous immunizations with GP-OVA were compared with those in C57BL/6J mice following subcutaneous immunizations with OVA absorbed onto the adjuvant alum (Alum/OVA). Vaccination with GP-OVA stimulated substantially higher antigen-specific CD4(+) T-cell lymphoproliferative and enzyme-linked immunospot (ELISPOT) responses than that with Alum/OVA. Moreover, the T-cell responses induced by GP-OVA were Th1 biased (determined by gamma interferon [IFN-gamma] ELISPOT assay) and Th17 biased (determined by interleukin-17a [IL-17a] ELISPOT assay). Finally, both the GP-OVA and Alum/OVA formulations induced strong secretions of IgG1 subclass anti-OVA antibodies, although only GP-OVA induced secretion of Th1-associated IgG2c antibodies. Thus, the GP-based vaccine platform combines adjuvanticity and antigen delivery to induce strong humoral and Th1- and Th17-biased CD4(+) T-cell responses.
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DOI of Published Version
Huang, H., G. R. Ostroff, C. K. Lee, C. A. Specht, and S. M. Levitz. 2010. Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded beta-glucan particles. mBio 1(3):e00164-10. doi:10.1128/mBio.00164-10.
Huang, Habin; Ostroff, Gary R.; Lee, Chrono K.; Specht, Charles A.; and Levitz, Stuart M., "Robust Stimulation of Humoral and Cellular Immune Responses following Vaccination with Antigen-Loaded beta-Glucan Particles" (2010). Infectious Diseases and Immunology Publications and Presentations. 43.