title: Antigen delivery by lipid-enveloped PLGA microparticle vaccines mediated by in situ vesicle shedding.
abstract: Lipid-coated poly(lactide-co-glycolide) microparticles (LCMPs) consist of a solid polymer core wrapped by a surface lipid bilayer. Previous studies demonstrated that immunization with LCMPs surface-decorated with nanograms of antigen elicit potent humoral immune responses in mice. However, the mechanism of action for these vaccines remained unclear, as LCMPs are too large to drain efficiently to lymph nodes from the vaccination site. Here, we characterized the stability of the lipid envelope of LCMPs and discovered that in the presence of serum the lipid coating of the particles spontaneously delaminates, shedding antigen-displaying vesicles. Lipid delamination generated 180 nm liposomes in a temperature- and lipid/serum-dependent manner. Vesicle shedding was restricted by inclusion of high-TM lipids or cholesterol in the LCMP coating. Administration of LCMPs bearing stabilized lipid envelopes generated weaker antibody responses than those of shedding-competent LCMPs, suggesting that in situ release of antigen-loaded vesicles plays a key role in the remarkable potency of LCMPs as vaccine adjuvants.
authors.affiliation: Department of Biological Engineering, ‡Department of Materials Science and Engineering, §Health Sciences and Technology Program, and ∥David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Melissa C
authors.initials: MC
authors.lastname: Hanson
authors.forename: Anna
authors.initials: A
authors.lastname: Bershteyn
authors.forename: Monica P
authors.initials: MP
authors.lastname: Crespo
authors.forename: Darrell J
authors.initials: DJ
authors.lastname: Irvine
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D020099:Coated Materials, Biocompatible / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D019344:Lactic Acid / Q000737:chemistry* / Q000494:pharmacology; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D014612:Vaccines / Q000737:chemistry*
chemical_list: D000276:Adjuvants, Immunologic; D020099:Coated Materials, Biocompatible; D008081:Liposomes; D011108:Polymers; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid