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dc.contributor.authorFriedrich, Nikolas
dc.contributor.authorStiegeler, Emanuel
dc.contributor.authorGlögl, Matthias
dc.contributor.authorLemmin, Thomas
dc.contributor.authorHansen, Simon
dc.contributor.authorKadelka, Claus
dc.contributor.authorWu, Yufan
dc.contributor.authorErnst, Patrick
dc.contributor.authorMaliqi, Liridona
dc.contributor.authorFoulkes, Caio
dc.contributor.authorMorin, Mylène
dc.contributor.authorEroglu, Mustafa
dc.contributor.authorLiechti, Thomas
dc.contributor.authorIvan, Branislav
dc.contributor.authorReinberg, Thomas
dc.contributor.authorSchaefer, Jonas V
dc.contributor.authorKarakus, Umut
dc.contributor.authorUrsprung, Stephan
dc.contributor.authorMann, Axel
dc.contributor.authorRusert, Peter
dc.contributor.authorKouyos, Roger D
dc.contributor.authorRobinson, John A
dc.contributor.authorGünthard, Huldrych F
dc.contributor.authorPlückthun, Andreas
dc.contributor.authorTrkola, Alexandra
dc.date.accessioned2021-11-22T14:45:24Z
dc.date.available2021-11-22T14:45:24Z
dc.date.issued2021-11-18
dc.date.submitted2021-01-25
dc.identifier.issn2041-1723
dc.identifier.others41467-021-27075-0
dc.identifier.other27075
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/330885
dc.descriptionFunder: Swiss government (through SERI) under grant agreement No.15.0337. Gilead HIV-1 Cure Grant 408 Clinical Priority Research Program of the University of Zurich Yvonne-Jacob Foundation Swiss HIV Cohort Study (SHCS) research foundation
dc.description.abstractThe V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base. Challenging this view, we present V3-crown directed broadly neutralizing Designed Ankyrin Repeat Proteins (bnDs) matching the breadth of V3-base bnAbs. While most bnAbs target prefusion Env, V3-crown bnDs bind open Env conformations triggered by CD4 engagement. BnDs achieve breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3. We further show that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth. Our results indicate a role of V3-crown responses and its conformational preferences in bnAb development to be considered in preventive and therapeutic approaches.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/45/612/1256
dc.subject/631/45/535/1266
dc.subject/631/250/2152/2153/1291
dc.subject/631/326/596/1296
dc.subject/692/699/255/1901
dc.subject/13/1
dc.subject/145
dc.subject/13/31
dc.subject/49/47
dc.subject/38/70
dc.subjectarticle
dc.titleDistinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.
dc.typeArticle
dc.date.updated2021-11-22T14:45:23Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume12
dc.identifier.doi10.17863/CAM.78328
dcterms.dateAccepted2021-11-03
rioxxterms.versionofrecord10.1038/s41467-021-27075-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFriedrich, Nikolas [0000-0003-0694-657X]
dc.contributor.orcidKadelka, Claus [0000-0002-5712-8529]
dc.contributor.orcidErnst, Patrick [0000-0001-6037-1856]
dc.contributor.orcidUrsprung, Stephan [0000-0003-2476-178X]
dc.contributor.orcidKouyos, Roger D [0000-0002-9220-8348]
dc.contributor.orcidRobinson, John A [0000-0001-7857-8556]
dc.contributor.orcidGünthard, Huldrych F [0000-0002-1142-6723]
dc.contributor.orcidPlückthun, Andreas [0000-0003-4191-5306]
dc.contributor.orcidTrkola, Alexandra [0000-0003-1013-876X]
dc.identifier.eissn2041-1723
pubs.funder-project-idSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) (314730_152663, 314730_172790, 324730B_179571, PZ00P3-142411, BSSGI0_155851, CRSK-3_190705, 310030_192689, 310030B_166676, 31003A_146278, 33CS30_148522)
pubs.funder-project-idEC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (681032)
cam.issuedOnline2021-11-18


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