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dc.contributor.authorWang, Shenshen
dc.contributor.authorMata-Fink, Jordi
dc.contributor.authorKriegsman, Barry
dc.contributor.authorIrvine, Darrell J.
dc.contributor.authorEisen, Herman N.
dc.contributor.authorBurton, Dennis R.
dc.contributor.authorKardar, Mehran
dc.contributor.authorChakraborty, Arup K.
dc.contributor.authorWittrup, Karl Dane
dc.contributor.authorEisen, Herman N.
dc.contributor.authorHanson, Melissa Catherine
dc.contributor.authorIrvine, Darrell J
dc.contributor.authorChakraborty, Arup K
dc.date.accessioned2016-03-24T14:57:45Z
dc.date.available2016-03-24T14:57:45Z
dc.date.issued2015-02
dc.date.submitted2014-10
dc.identifier.issn00928674
dc.identifier.issn1097-4172
dc.identifier.urihttp://hdl.handle.net/1721.1/101768
dc.description.abstractGeneration of potent antibodies by a mutation-selection process called affinity maturation is a key component of effective immune responses. Antibodies that protect against highly mutable pathogens must neutralize diverse strains. Developing effective immunization strategies to drive their evolution requires understanding how affinity maturation happens in an environment where variants of the same antigen are present. We present an in silico model of affinity maturation driven by antigen variants which reveals that induction of cross-reactive antibodies often occurs with low probability because conflicting selection forces, imposed by different antigen variants, can frustrate affinity maturation. We describe how variables such as temporal pattern of antigen administration influence the outcome of this frustrated evolutionary process. Our calculations predict, and experiments in mice with variant gp120 constructs of the HIV envelope protein confirm, that sequential immunization with antigen variants is preferred over a cocktail for induction of cross-reactive antibodies focused on the shared CD4 binding site epitope.en_US
dc.description.sponsorshipRagon Institute of MGH, MIT and Harvarden_US
dc.description.sponsorshipCenter for HIV/AIDS Vaccine Immunology and Immunogen Discovery (Grant UM1AI100663)en_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2015.01.027en_US
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivs Licenseen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleManipulating the Selection Forces during Affinity Maturation to Generate Cross-Reactive HIV Antibodiesen_US
dc.typeArticleen_US
dc.identifier.citationWang, Shenshen, Jordi Mata-Fink, Barry Kriegsman, Melissa Hanson, Darrell J. Irvine, Herman N. Eisen, Dennis R. Burton, K. Dane Wittrup, Mehran Kardar, and Arup K. Chakraborty. “Manipulating the Selection Forces During Affinity Maturation to Generate Cross-Reactive HIV Antibodies.” Cell 160, no. 4 (February 2015): 785–797.en_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Physicsen_US
dc.contributor.departmentRagon Institute of MGH, MIT and Harvarden_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.contributor.mitauthorWang, Shenshenen_US
dc.contributor.mitauthorMata-Fink, Jordien_US
dc.contributor.mitauthorKriegsman, Barryen_US
dc.contributor.mitauthorHanson, Melissaen_US
dc.contributor.mitauthorIrvine, Darrell J.en_US
dc.contributor.mitauthorEisen, Herman N.en_US
dc.contributor.mitauthorWittrup, Karl Daneen_US
dc.contributor.mitauthorKardar, Mehranen_US
dc.contributor.mitauthorChakraborty, Arup K.en_US
dc.relation.journalCellen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsWang, Shenshen; Mata-Fink, Jordi; Kriegsman, Barry; Hanson, Melissa; Irvine, Darrell J.; Eisen, Herman N.; Burton, Dennis R.; Wittrup, K. Dane; Kardar, Mehran; Chakraborty, Arup K.en_US
dc.identifier.orcidhttps://orcid.org/0000-0003-2398-5896
dc.identifier.orcidhttps://orcid.org/0000-0002-6064-0531
dc.identifier.orcidhttps://orcid.org/0000-0003-1268-9602
dc.identifier.orcidhttps://orcid.org/0000-0002-1112-5912
mit.licensePUBLISHER_CCen_US


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