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dc.contributor.authorJewell, Christopher M.
dc.contributor.authorIrvine, Darrell J.
dc.contributor.authorBustamante Lopez, Sandra C.
dc.date.accessioned2012-04-13T16:47:46Z
dc.date.available2012-04-13T16:47:46Z
dc.date.issued2010-09
dc.date.submitted2011-04
dc.identifier.issn1091-6490
dc.identifier.urihttp://hdl.handle.net/1721.1/70020
dc.description.abstractRecent studies have demonstrated a simple, potentially universal strategy to enhance vaccine potency, via intralymph node (i.LN) injection. To date, intranodal immunization studies have focused on the delivery of unadjuvanted vaccines (e.g., naked DNA, peptide, or protein). We hypothesized that combining i.LN vaccination with controlled release biomaterials permitting sustained dosing of molecular adjuvants to the local tissue microenvironment would further enhance this promising vaccination strategy. To test this idea, we encapsulated the Toll-like receptor-3 ligand poly(inosinic:cytidylic acid) (polyIC) in biodegradable poly(lactide-co-glycolide) microparticles (MPs) designed to remain extracellular and release polyIC in the LN over several days. Intranodal injection of MPs increased persistence of polyIC in LNs compared to the same dose of soluble polyIC or polyIC formulated in nanoparticles, leading to increased accumulation of Toll-like receptor agonist in LN-resident antigen presenting cells and more enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin-specific T cells to frequencies as high as 18% among all CD8[superscript +] cells following a single injection (8.2-fold greater than the same vaccine given i.m.), a response that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a 10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release-formulated adjuvants may be a broadly applicable strategy to enhance therapeutic or prophylactic vaccines.
dc.description.sponsorshipMassachusetts Institute of Technology. Ragon Institute of MGH, MIT and Harvard (Ragon Institute Postdoctoral Fellow)
dc.description.sponsorshipHoward Hughes Medical Institute (Investigator)
dc.language.isoen_US
dc.publisherNational Academy of Sciences
dc.relation.isversionofhttp://dx.doi.org/10.1073/pnas.1105200108en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourcePNASen_US
dc.titleIn situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particlesen_US
dc.typeArticleen_US
dc.identifier.citationJewell, C. M., S. C. Bustamante Lopez, and D. J. Irvine. “In Situ Engineering of the Lymph Node Microenvironment via Intranodal Injection of Adjuvant-releasing Polymer Particles.” Proceedings of the National Academy of Sciences 108.38 (2011): 15745–15750.
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Materials Science and Engineeringen_US
dc.contributor.departmentRagon Institute of MGH, MIT and Harvarden_US
dc.contributor.approverIrvine, Darrell J.
dc.contributor.mitauthorJewell, Christopher M.
dc.contributor.mitauthorBustamante Lopez, Sandra C.
dc.contributor.mitauthorIrvine, Darrell J.
dc.relation.journalProceedings of the National Academy of Sciences
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsJewell, C. M.; Bustamante Lopez, S. C.; Irvine, D. J.en
mit.licensePUBLISHER_POLICYen_US


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