A Protective Vaccine Delivery System for In Vivo T Cell Stimulation Using Nanoengineered Polymer Hydrogel Capsules
Open Access
- 13 October 2009
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 3 (11), 3391-3400
- https://doi.org/10.1021/nn900715g
Abstract
Successful delivery of labile vaccine antigens, such as peptides and proteins, to stimulate CD4 and CD8 T cell immunity could improve vaccine strategies against chronic infections such as HIV and Hepatitis C. Layer-by-layer (LbL)-assembled nanoengineered hydrogel capsules represent a novel and promising technology for the protection and delivery of labile vaccine candidates to antigen-presenting cells (APCs). Here we report on the in vitro and in vivo immunostimulatory capabilities of LbL-assembled disulfide cross-linked poly(methacrylic acid) (PMASH) hydrogel capsules as a delivery strategy for protein and peptide vaccines using robust transgenic mice models and ovalbumin (OVA) as a model vaccine. We demonstrate that OVA protein as well as multiple OVA peptides can be successfully encapsulated within nanoengineered PMASH hydrogel capsules. OVA-containing PMASH capsules are internalized by mouse APCs, resulting in presentation of OVA epitopes and subsequent activation of OVA-specific CD4 and CD8 T cells in vitro. OVA-specific CD4 and CD8 T cells are also activated to proliferate in vivo following intravenous vaccination of mice with OVA protein- and OVA peptide-loaded PMASH hydrogel capsules. Furthermore, we show that OVA encapsulated within the PMASH capsules resulted in at least 6-fold greater proliferation of OVA-specific CD8 T cells and 70-fold greater proliferation of OVA-specific CD4 T cells in vivo compared to the equivalent amount of OVA protein administered alone. These results highlight the potential of nanoengineered hydrogel capsules for vaccine delivery.Keywords
This publication has 31 references indexed in Scilit:
- Polymeric Microcapsules for Synthetic ApplicationsMacromolecular Bioscience, 2008
- Detailed Analysis Concerning the Biodistribution and Metabolism of Human Calcitonin-Derived Cell-Penetrating PeptidesBioconjugate Chemistry, 2008
- Control of Viremia and Prevention of AIDS following Immunotherapy of SIV-Infected Macaques with Peptide-Pulsed BloodPLoS Pathogens, 2008
- POLYMERSOMESAnnual Review of Biomedical Engineering, 2006
- Recent advances with liposomes as pharmaceutical carriersNature Reviews Drug Discovery, 2005
- HCV Persistence and Immune Evasion in the Absence of Memory T Cell HelpScience, 2003
- Block copolymer micelles for drug delivery: design, characterization and biological significanceAdvanced Drug Delivery Reviews, 2001
- The role of CD4+ T helper cells in the cytotoxic T lymphocyte response to HIV-1Current Opinion in Immunology, 2000
- The Critical Need for CD4 Help in Maintaining Effective Cytotoxic T Lymphocyte ResponsesThe Journal of Experimental Medicine, 1998
- Novel Hollow Polymer Shells by Colloid-Templated Assembly of PolyelectrolytesAngewandte Chemie-International Edition, 1998