University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology; Program in Molecular Medicine

Publication Date

10-1-2013

Document Type

Article

Subjects

Animals; CD4-Positive T-Lymphocytes; Cytokines; Drug Carriers; Glucans; Immunoglobulin G; Mice; Mice, Inbred C57BL; Ovalbumin; Saccharomyces cerevisiae; Vaccination; Vaccines

Disciplines

Immunity | Immunoprophylaxis and Therapy | Medical Immunology | Medicinal-Pharmaceutical Chemistry

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.

Rights and Permissions

Citation: 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

Comments

Copyright © 2013, American Society for Microbiology. All Rights Reserved. Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Clinical and vaccine immunology : CVI

PubMed ID

23945157

Share

COinS
 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.