{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:38:04Z","timestamp":1792143484552,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011601","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000}}],"reference-count":159,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T00:00:00Z","timestamp":1698624000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI036082"],"award-info":[{"award-number":["AI036082"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01 AI110657"],"award-info":[{"award-number":["P01 AI110657"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000866","name":"International AIDS Vaccine Initiative","doi-asserted-by":"publisher","award":["INV-008352\/OPP1153692"],"award-info":[{"award-number":["INV-008352\/OPP1153692"]}],"id":[{"id":"10.13039\/100000866","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Neutralizing antibodies (NAbs) to multiple epitopes on the HIV-1-envelope glycoprotein (Env) have been isolated from infected persons. The potency of NAbs is measured more often than the size of the persistent fraction\n                    <jats:italic>o<\/jats:italic>\n                    f infectivity at maximum neutralization, which may also influence preventive efficacy of active or passive immunization and the therapeutic outcome of the latter. Many NAbs neutralize HIV-1 CZA97.012, a clone of a Clade-C isolate, to ~100%. But here NAb PGT151, directed to a fusion-peptide epitope, left a persistent fraction of 15%. NAb PGT145, ligating the Env-trimer apex, left no detectable persistent fraction. The divergence in persistent fractions was further analyzed by depletion of pseudoviral populations of the most PGT151- and PGT145-reactive virions. Thereby, neutralization by the non-depleting NAb increased, whereas neutralization by the depleting NAb decreased. Furthermore, depletion by PGT151 increased sensitivity to autologous neutralization by sera from rabbits immunized with soluble native-like CZA97.012 trimer: substantial persistent fractions were reduced. NAbs in these sera target epitopes comprising residue D411 at the V4-\u03b219 transition in a defect of the glycan shield on CZA97.012 Env. NAb binding to affinity-fractionated soluble native-like CZA97.012 trimer differed commensurately with neutralization in analyses by ELISA and surface plasmon resonance. Glycan differences between PGT151- and PGT145-purified trimer fractions were then demonstrated by mass spectrometry, providing one explanation for the differential antigenicity. These differences were interpreted in relation to a new structure at 3.4-\u00c5 resolution of the soluble CZA97.012 trimer determined by cryo-electron microscopy. The trimer adopted a closed conformation, refuting apex opening as the cause of reduced PGT145 binding to the PGT151-purified form. The evidence suggests that differences in binding and neutralization after trimer purification or pseudovirus depletion with PGT145 or PGT151 are caused by variation in glycosylation, and that some glycan variants affect antigenicity through direct effects on antibody contacts, whereas others act allosterically.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011601","type":"journal-article","created":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T14:08:30Z","timestamp":1698674910000},"page":"e1011601","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":12,"title":["Glycan heterogeneity as a cause of the persistent fraction in HIV-1 neutralization"],"prefix":"10.1371","volume":"19","author":[{"given":"Rajesh P.","family":"Ringe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Colin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Ozorowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anila","family":"Yasmeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma E.","family":"Seabright","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Hyun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"Antanasijevic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimmo","family":"Rantalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Ketas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Ward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Crispin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8222-278X","authenticated-orcid":true,"given":"P. J.","family":"Klasse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,30]]},"reference":[{"key":"ppat.1011601.ref001","first-page":"2014","article-title":"Neutralization of Virus Infectivity by Antibodies: Old Problems in New Perspectives.","author":"PJ Klasse","year":"2014","journal-title":"Adv Biol."},{"issue":"1","key":"ppat.1011601.ref002","doi-asserted-by":"crossref","first-page":"e52","DOI":"10.1016\/S2666-5247(21)00267-6","article-title":"Neutralising antibody titres as predictors of protection against SARS-CoV-2 variants and the impact of boosting: a meta-analysis","volume":"3","author":"D Cromer","year":"2022","journal-title":"Lancet Microbe"},{"issue":"9","key":"ppat.1011601.ref003","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/nri891","article-title":"Antibodies, viruses and vaccines","volume":"2","author":"DR Burton","year":"2002","journal-title":"Nat Rev Immunol"},{"issue":"7","key":"ppat.1011601.ref004","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"SA Plotkin","year":"2010","journal-title":"Clin Vaccine Immunol"},{"issue":"8","key":"ppat.1011601.ref005","doi-asserted-by":"crossref","first-page":"e0003422","DOI":"10.1128\/jvi.00034-22","article-title":"Reappraising the Value of HIV-1 Vaccine Correlates of Protection Analyses","volume":"96","author":"PJ Klasse","year":"2022","journal-title":"J Virol"},{"key":"ppat.1011601.ref006","doi-asserted-by":"crossref","first-page":"1081107","DOI":"10.3389\/fimmu.2022.1081107","article-title":"Recent updates on correlates of vaccine-induced protection.","volume":"13","author":"SA Plotkin","year":"2022","journal-title":"Front Immunol"},{"key":"ppat.1011601.ref007","first-page":"1","article-title":"Antiviral neutralizing antibodies: from in vitro to in vivo activity","author":"DR Burton","year":"2023","journal-title":"Nat Rev Immunol"},{"issue":"11","key":"ppat.1011601.ref008","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a030262","article-title":"What Are the Most Powerful Immunogen Design Vaccine Strategies? 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