Antigen Delivery by Lipid-Enveloped PLGA Microparticle Vaccines Mediated by in Situ Vesicle Shedding
Author(s)Hanson, Melissa C.; Bershteyn, Anna; Crespo, Monica P.; Irvine, Darrell J.
MetadataShow full item record
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-T[subscript M] 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.
DepartmentDavid H. Koch Institute for Integrative Cancer Research at MIT; Harvard University--MIT Division of Health Sciences and Technology; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Materials Science and Engineering; Ragon Institute of MGH, MIT and Harvard
American Chemical Society (ACS)
Hanson, Melissa C., Anna Bershteyn, Monica P. Crespo, and Darrell J. Irvine. “Antigen Delivery by Lipid-Enveloped PLGA Microparticle Vaccines Mediated by in Situ Vesicle Shedding.” Biomacromolecules 15, no. 7 (July 14, 2014): 2475–2481. © 2014 American Chemical Society
Final published version