Journal
ACS Applied Materials & Interfaces
Volume 8, Issue 29, Pages 18722-18731Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.6b06275
Keywords
rational design; immunology; self-assembly; vaccine; polyelectrolyte multilayer
Funding
- NSF [1351688]
- University of Maryland Division of Research
- NIH [T32 CA154274, T32 AI089621]
- Alex's Lemonade Stand Foundation
- American Association of Pharmaceutical Scientists Foundation
- NSF Graduate Research Fellowship Program [DGE1322106]
- Damon Runyon Foundation [DRR3415]
- Alliance for Cancer Gene Therapy [15051543]
- Melanoma Research Alliance [348963]
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [1351688] Funding Source: National Science Foundation
Ask authors/readers for more resources
While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen-specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available