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dc.contributor.authorSangesland, Maya
dc.contributor.authorRonsard, Larance
dc.contributor.authorKazer, Samuel Weisgurt
dc.contributor.authorBals, Julia
dc.contributor.authorBoyoglu-Barnum, Seyhan
dc.contributor.authorYousif, Ashraf S.
dc.contributor.authorBarnes, Ralston
dc.contributor.authorFeldman, Jared
dc.contributor.authorQuirindongo-Crespo, Maricel
dc.contributor.authorMcTamney, Patrick M.
dc.contributor.authorRohrer, Daniel
dc.contributor.authorLonberg, Nils
dc.contributor.authorChackerian, Bryce
dc.contributor.authorGraham, Barney S.
dc.contributor.authorKanekiyo, Masaru
dc.contributor.authorShalek, Alexander K
dc.contributor.authorLingwood, Daniel
dc.date.accessioned2020-10-30T17:10:54Z
dc.date.available2020-10-30T17:10:54Z
dc.date.issued2019-10
dc.date.submitted2019-05
dc.identifier.issn1074-7613
dc.identifier.urihttps://hdl.handle.net/1721.1/128273
dc.description.abstractAntibody paratopes are formed by hypervariable complementarity-determining regions (CDRH3s) and variable gene-encoded CDRs. The latter show biased usage in human broadly neutralizing antibodies (bnAbs) against both HIV and influenza virus, suggesting the existence of gene-endowed targeting solutions that may be amenable to pathway amplification. To test this, we generated transgenic mice with human CDRH3 diversity but simultaneously constrained to individual user-defined human immunoglobulin variable heavy-chain (VH) genes, including IGHV1-69, which shows biased usage in human bnAbs targeting the hemagglutinin stalk of group 1 influenza A viruses. Sequential immunization with a stalk-only hemagglutinin nanoparticle elicited group 1 bnAbs, but only in IGHV1-69 mice. This VH-endowed response required minimal affinity maturation, was elicited alongside pre-existing influenza immunity, and when IGHV1-69 B cells were diluted to match the frequency measured in humans. These results indicate that the human repertoire could, in principle, support germline-encoded bnAb elicitation using a single recombinant hemagglutinin immunogen.en_US
dc.description.sponsorshipNIH (Grants 1DP2OD020839, 2U19AI089992, 1U54CA217377, P01AI039671, 5U24AI118672, 2RM1HG006193, 1R33CA202820, 2R01HL095791, 1R01AI138546, 1R01HL126554, 1R01DA046277, 2R01HL095791)en_US
dc.description.sponsorshipBill and Melinda Gates Foundation (Grants OPP1139972 and BMGF OPP1116944)en_US
dc.language.isoen
dc.publisherElsevier BVen_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.immuni.2019.09.001en_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.titleGermline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virusen_US
dc.typeArticleen_US
dc.identifier.citationSangesland, Maya et al. "Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virus." Immunity 51, 4 (October 2019): P735-749.e8 © 2019 Elsevieren_US
dc.contributor.departmentMassachusetts Institute of Technology. Institute for Medical Engineering & Scienceen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Chemistryen_US
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.contributor.departmentKoch Institute for Integrative Cancer Research at MITen_US
dc.relation.journalImmunityen_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
dc.date.updated2020-10-19T15:10:45Z
dspace.orderedauthorsSangesland, M; Ronsard, L; Kazer, SW; Bals, J; Boyoglu-Barnum, S; Yousif, AS; Barnes, R; Feldman, J; Quirindongo-Crespo, M; McTamney, PM; Rohrer, D; Lonberg, N; Chackerian, B; Graham, BS; Kanekiyo, M; Shalek, AK; Lingwood, Den_US
dspace.date.submission2020-10-19T15:10:54Z
mit.journal.volume51en_US
mit.journal.issue4en_US
mit.licensePUBLISHER_CC


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