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dc.contributor.advisorLaura L. Kiessling.en_US
dc.contributor.authorJarvis, Cassie Marie.en_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemistry.en_US
dc.date.accessioned2020-10-18T21:36:49Z
dc.date.available2020-10-18T21:36:49Z
dc.date.copyright2019en_US
dc.date.issued2020en_US
dc.identifier.urihttps://hdl.handle.net/1721.1/128069
dc.descriptionThesis: Ph. D., Massachusetts Institute of Technology, Department of Chemistry, 2020en_US
dc.descriptionCataloged from the PDF of thesis. "February 2020."en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractMultivalent carbohydrate interactions play a critical role in many immunological processes, including pathogen recognition and immune activation. Synthetic polymers can mimic multivalent glycans and probe different facets of immunity to ultimately inform the design of effective vaccines. In Chapter 1, I review how antigen physical properties and lectin signaling can direct dendritic cell (DC)-mediated immune responses. The DC lectin DC-SIGN is involved in both immune activation and evasion. In Chapter 2, I generated glycopolymers bearing a multivalent display of a DC-SIGN-targeting aryl mannoside ligand to investigate how antigen features influence DC-SIGN-mediated responses. Specifically, I found that antigen size alters trafficking through DCSIGN. Large polymer aggregates were trafficked to the same subcellular DC reservoirs that harbor HIV, whereas small soluble polymers were routed to endosomes.en_US
dc.description.abstractIn light of these findings, in Chapter 3 we designed a nanoparticle vaccine platform using the same aryl mannoside ligand to efficiently target antigen to DC-SIGN for endosomal routing and antigen presentation. Functionalized bacteriophage Q[beta] virus-like particles elicited DC-mediated proinflammatory Th1-type immune responses, which are effective against intracellular pathogens and tumors. As many vaccines function by generating neutralizing antibodies, we used polymeric antigens to interrogate B cell activation. In Chapter 4, I used ROMP polymers to target B cells and systematically evaluated key antigen features that promote B cell activation and antibody production. The most robust responses were induced by polymers with a high valency of B and T cell epitopes where the T cell epitope is readily liberated upon endosomal processing. Optimal polymer designs stimulated more robust B cell activation than a comparable protein conjugate.en_US
dc.description.abstractOverall, my thesis work identified numerous antigen parameters that can be tuned to direct and optimize DC and B cell activation for the design of effective targeted synthetic vaccines.en_US
dc.description.statementofresponsibilityby Cassie Marie Jarvis.en_US
dc.format.extent168 pagesen_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsMIT theses may be protected by copyright. Please reuse MIT thesis content according to the MIT Libraries Permissions Policy, which is available through the URL provided.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemistry.en_US
dc.titlePolymeric antigens as targeted probes of immunityen_US
dc.typeThesisen_US
dc.description.degreePh. D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.identifier.oclc1199083213en_US
dc.description.collectionPh.D. Massachusetts Institute of Technology, Department of Chemistryen_US
dspace.imported2020-10-18T21:36:45Zen_US
mit.thesis.degreeDoctoralen_US
mit.thesis.departmentChemen_US


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