title: A protective vaccine delivery system for in vivo T cell stimulation using nanoengineered polymer hydrogel capsules.
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) (PMA(SH)) 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 PMA(SH) hydrogel capsules. OVA-containing PMA(SH) 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(SH) hydrogel capsules. Furthermore, we show that OVA encapsulated within the PMA(SH) 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.
authors.affiliation: Department of Microbiology & Immunology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Sexton
authors.forename: Paul G
authors.initials: PG
authors.lastname: Whitney
authors.forename: Siow-Feng
authors.initials: SF
authors.lastname: Chong
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Zelikin
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: Frank
authors.initials: F
authors.lastname: Caruso
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001692:Biological Transport; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002214:Capsules; D049109:Cell Proliferation; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry*; D007114:Immunization; D042541:Intracellular Space / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D036103:Nanotechnology; D010047:Ovalbumin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014612:Vaccines / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D002214:Capsules; D004337:Drug Carriers; D020100:Hydrogels; D010446:Peptide Fragments; D011109:Polymethacrylic Acids; D011948:Receptors, Antigen, T-Cell; D014612:Vaccines; D010047:Ovalbumin