Show simple item record

dc.contributor.advisorK. Dane Wittrup.en_US
dc.contributor.authorMata-Fink, Jordien_US
dc.contributor.otherMassachusetts Institute of Technology. Department of Chemical Engineering.en_US
dc.date.accessioned2013-06-17T19:46:33Z
dc.date.available2013-06-17T19:46:33Z
dc.date.issued2013en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/79194
dc.descriptionThesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, February 2013.en_US
dc.descriptionCataloged from PDF version of thesis. "February 2013."en_US
dc.descriptionIncludes bibliographical references.en_US
dc.description.abstractThe sequence diversity of glycoprotein gp120 of the envelope spike of Human Immunodeficiency Virus (HIV) allows the virus to escape from antibody selection pressure. Certain conserved epitopes, like the CD4 binding site, are required for viral fitness and antibodies against these epitopes are able to neutralize HIV from multiple clades. Passive immunization experiments suggest that eliciting such broadly reactive antibodies by vaccination may provide protection, but so far this has proven impossible. In this thesis, we establish a yeast surface display system for the development of gp120-based molecules for antibody characterization and immunogen design. A stripped core gp120 is constructed that retains the correct presentation of the CD4 binding site. Epitopes of several CD4 binding site-directed antibodies, including the gold standard antibody VRC01, are mapped with yeast displayed mutant libraries. A panel of immunogens that share the epitope defined by VRC01 but are diverse elsewhere on their surfaces is designed. Mice immunized sequentially with the diverse immunogens elicit an antibody response that is focused entirely on the VRC01 epitope. The serum cross-reacts with gp120 from multiple clades. Monoclonal antibodies from these mice are isolated and characterized.en_US
dc.description.statementofresponsibilityby Jordi Mata-Fink.en_US
dc.format.extent147 p.en_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.en_US
dc.rights.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectChemical Engineering.en_US
dc.titleEngineering of HIV gp120 by yeast surface display for neutralizing antibody characterization and immunogen designen_US
dc.title.alternativeEngineering of Human Immunodeficiency Virus gp120 by yeast surface display for neutralizing antibody characterization and immunogen designen_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineering.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineering
dc.identifier.oclc844350724en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record