Characterization and Optimization of the Glucan Particle-Based Vaccine Platform

Abstract

bGlucan particles (GPs) are hollow porous Saccharomyces cerevisiae cell walls that are treated so that they are composed primarily of ␤-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 ؋ 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-␥), interleukin 17A (IL-17A), and dual IFN-␥/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.

Recent advances in oral vaccine development

“…The most crucial cellular players, antibody and T-cell mediated responses upon β-glucan microparticulate internalization are depicted in Figure 4. This is in agreement with a study performed by Huang et al 109 wherein subcutaneous administrations of GP formulations elicited strong antigenspecific antibody and T-cell responses, including the production of IFN-γ and IL17a by CD4 + Th1 and Th17 cells.…”

Exploiting fungal cell wall components in vaccines

“…Mice were vaccinated with GPs containing OVA trapped with: 1) yeast RNA; 2) alginate calcium; and 3) alginate calcium plus chitosan. Robust antigen-specific CD4 + T cell and antibody responses were seen regardless of the trapping materials utilized (26). Note that alginate calcium and chitosan are approved by the United States Food and Drug Administration and generally regarded as safe (27, 28).…”

Surface-modified yeast cells: A novel eukaryotic carrier for oral application

“…It is taken up by M cells [36] and is known to possess adjuvant effects by stimulating innate immune responses by structural cell wall components [20,41,42]. In particular, yeast is able to stimulate TLR2 and 4 which have been shown to enhance microparticle uptake by M cells and to support mucosal adjuvantic properties of a carrier [2,43,44].…”