A protective vaccine delivery system for in vivo T cell stimulation using nanoengineered polymer hydrogel capsules

Amy Sexton, Paul G Whitney, Siow-Feng Chong, Alexander N Zelikin, Angus Johnston, Robert De Rose, Andrew G Brooks, Frank Caruso, Stephen J Kent

Research output: Contribution to journalArticleResearchpeer-review

143 Citations (Scopus)

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 PMA SHhydrogel 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.
Original languageEnglish
Pages (from-to)3391 - 3400
Number of pages10
JournalACS Nano
Volume3
Issue number11
DOIs
Publication statusPublished - 2009
Externally publishedYes

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