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dc.contributor.authorTsioris, Konstantinos
dc.contributor.authorGupta, Namita T.
dc.contributor.authorOgunniyi, Adebola Oluwakayode
dc.contributor.authorQian, Feng
dc.contributor.authorYao, Yi
dc.contributor.authorWang, Xiaomei
dc.contributor.authorStern, Joel N. H.
dc.contributor.authorChari, Raj
dc.contributor.authorBriggs, Adrian W.
dc.contributor.authorClouser, Christopher R.
dc.contributor.authorVigneault, Francois
dc.contributor.authorChurch, George M.
dc.contributor.authorGarcia, Melissa N.
dc.contributor.authorMurray, Kristy O.
dc.contributor.authorMontgomery, Ruth R.
dc.contributor.authorKleinstein, Steven H.
dc.contributor.authorLove, J. Christopher
dc.contributor.authorZimnisky, Ross Martin
dc.contributor.authorLove, J. Christopher
dc.date.accessioned2016-02-19T02:59:08Z
dc.date.available2016-02-19T02:59:08Z
dc.date.issued2015-10
dc.date.submitted2015-06
dc.identifier.issn1757-9694
dc.identifier.issn1757-9708
dc.identifier.urihttp://hdl.handle.net/1721.1/101221
dc.description.abstractWest Nile virus (WNV) infection is an emerging mosquito-borne disease that can lead to severe neurological illness and currently has no available treatment or vaccine. Using microengraving, an integrated single-cell analysis method, we analyzed a cohort of subjects infected with WNV – recently infected and post-convalescent subjects – and efficiently identified four novel WNV neutralizing antibodies. We also assessed the humoral response to WNV on a single-cell and repertoire level by integrating next generation sequencing (NGS) into our analysis. The results from single-cell analysis indicate persistence of WNV-specific memory B cells and antibody-secreting cells in post-convalescent subjects. These cells exhibited class-switched antibody isotypes. Furthermore, the results suggest that the antibody response itself does not predict the clinical severity of the disease (asymptomatic or symptomatic). Using the nucleotide coding sequences for WNV-specific antibodies derived from single cells, we revealed the ontogeny of expanded WNV-specific clones in the repertoires of recently infected subjects through NGS and bioinformatic analysis. This analysis also indicated that the humoral response to WNV did not depend on an anamnestic response, due to an unlikely previous exposure to the virus. The innovative and integrative approach presented here to analyze the evolution of neutralizing antibodies from natural infection on a single-cell and repertoire level can also be applied to vaccine studies, and could potentially aid the development of therapeutic antibodies and our basic understanding of other infectious diseases.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (U19AI089992)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (AI091816)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (R01AI104739)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (1F32AI112359-01)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (T15LM07056)en_US
dc.description.sponsorshipHuman Immunology Project Consortiumen_US
dc.description.sponsorshipGillson Longenbaugh Foundationen_US
dc.language.isoen_US
dc.publisherRoyal Society of Chemistryen_US
dc.relation.isversionofhttp://dx.doi.org/10.1039/c5ib00169ben_US
dc.rightsCreative Commons Attribution 3.0 Unported licenceen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.sourceRoyal Society of Chemistryen_US
dc.titleNeutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencingen_US
dc.typeArticleen_US
dc.identifier.citationTsioris, Konstantinos, Namita T. Gupta, Adebola O. Ogunniyi, Ross M. Zimnisky, Feng Qian, Yi Yao, Xiaomei Wang, et al. “Neutralizing Antibodies Against West Nile Virus Identified Directly from Human B Cells by Single-Cell Analysis and Next Generation Sequencing.” Integr. Biol. 7, no. 12 (2015): 1587–1597. © 2015 Royal Society of Chemistryen_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemical Engineeringen_US
dc.contributor.mitauthorTsioris, Konstantinosen_US
dc.contributor.mitauthorOgunniyi, Adebola Oluwakayodeen_US
dc.contributor.mitauthorZimnisky, Ross Martinen_US
dc.contributor.mitauthorLove, J. Christopheren_US
dc.relation.journalIntegrative Biologyen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsTsioris, Konstantinos; Gupta, Namita T.; Ogunniyi, Adebola O.; Zimnisky, Ross M.; Qian, Feng; Yao, Yi; Wang, Xiaomei; Stern, Joel N. H.; Chari, Raj; Briggs, Adrian W.; Clouser, Christopher R.; Vigneault, Francois; Church, George M.; Garcia, Melissa N.; Murray, Kristy O.; Montgomery, Ruth R.; Kleinstein, Steven H.; Love, J. Christopheren_US
dc.identifier.orcidhttps://orcid.org/0000-0003-1387-8472
dc.identifier.orcidhttps://orcid.org/0000-0003-0921-3144
dspace.mitauthor.errortrue
mit.licensePUBLISHER_CCen_US


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