Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine
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
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.
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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.
DOI of Published Version
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
Clinical and vaccine immunology : CVI
Huang, Haibin; Ostroff, Gary R.; Lee, Chrono K.; Specht, Charles A.; and Levitz, Stuart M., "Characterization and optimization of the glucan particle-based vaccine platform" (2013). University of Massachusetts Medical School Faculty Publications. 762.