A paradigm for peptide vaccine delivery using viral epitopes encapsulated in degradable polymer hydrogel capsules.
We report on the use of degradable polymer capsules as carriers for the delivery of oligopeptide antigens to professional antigen presenting cells (APCs). To achieve encapsulation, oligopeptide sequences were covalently linked to a negatively charged carrier polymer via biodegradable linkages and the resulting conjugate was then adsorbed onto amine-functionalized silica particles. These peptide-coated particles were then used as templates for the layer-by-layer (LbL) deposition of thiolated poly(methacrylic acid) (PMA(SH)) and poly(vinylpyrrolidone) (PVPON) multilayers. Removal of the silica core and disruption of the hydrogen bonding between PMA(SH) and PVPON by altering the solution pH yielded disulfide-stabilized PMA capsules that retain the encapsulated cargo in an oxidative environment. In the presence of a natural reducing agent, glutathione, cleavage of the disulfide bonds causes release of the peptide from the capsules. The developed strategy provides control over peptide loading into polymer capsules and yields colloidally stable micron- and submicron-sized carriers with uniform size and peptide loading. The conjugation and encapsulation procedures were proven to be non-degrading to the peptide vaccines. The peptide-loaded capsules were successfully used to deliver their cargo to APCs and activate CD8 T lymphocytes in a non-human primate model of SIV infection ex vivo. The reported approach represents a novel paradigm in the delivery of peptide vaccines and other therapeutic agents.
Chong
Siow-Feng
SF
Centre for Nanoscience and Nanotechnology, Department of Chemical and Biomolecular Engineering, The University of Melbourne, Parkville, Victoria 3010, Australia.
Sexton
Amy
A
De Rose
Robert
R
Kent
Stephen J
SJ
Zelikin
Alexander N
AN
Caruso
Frank
F
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D003432:Cross-Linking Reagents; D004337:Drug Carriers / Q000737:chemistry*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007114:Immunization; D008251:Macaca; D011108:Polymers / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
D003432:Cross-Linking Reagents; D004337:Drug Carriers; D011108:Polymers; D011109:Polymethacrylic Acids; D022223:Vaccines, Subunit; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate