{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T21:20:43Z","timestamp":1772227243645,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010450","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000}}],"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U01AI136677"],"award-info":[{"award-number":["U01AI136677"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016962","name":"Department of Science and Innovation, South Africa","doi-asserted-by":"publisher","award":["98341"],"award-info":[{"award-number":["98341"]}],"id":[{"id":"10.13039\/100016962","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","award":["98341"],"award-info":[{"award-number":["98341"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006967","name":"Center for AIDS Research, Duke University","doi-asserted-by":"publisher","award":["A1067854"],"award-info":[{"award-number":["A1067854"]}],"id":[{"id":"10.13039\/100006967","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19 AI51794"],"award-info":[{"award-number":["U19 AI51794"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Broadly neutralizing antibodies (bNAbs) that target the membrane-proximal external region (MPER) of HIV gp41 envelope, such as 4E10, VRC42.01 and PGZL1, can neutralize &gt;80% of viruses. These three MPER-directed monoclonal antibodies share germline antibody genes (\n                    <jats:italic>IGHV1-69<\/jats:italic>\n                    and\n                    <jats:italic>IGKV3-20)<\/jats:italic>\n                    and form a bNAb epitope class. Furthermore, convergent evolution within these two lineages towards a\n                    <jats:sup>\n                      <jats:bold>111.2<\/jats:bold>\n                    <\/jats:sup>\n                    GW\n                    <jats:sup>\n                      <jats:bold>111.3<\/jats:bold>\n                    <\/jats:sup>\n                    motif in the CDRH3 is known to enhance neutralization potency. We have previously isolated an MPER neutralizing antibody, CAP206-CH12, that uses these same germline heavy and light chain genes but lacks breadth (neutralizing only 6% of heterologous viruses). Longitudinal sequencing of the CAP206-CH12 lineage over three years revealed similar convergent evolution towards\n                    <jats:sup>\n                      <jats:bold>111.2<\/jats:bold>\n                    <\/jats:sup>\n                    GW\n                    <jats:sup>\n                      <jats:bold>111.3<\/jats:bold>\n                    <\/jats:sup>\n                    among some lineage members. Mutagenesis of CAP206-CH12 from\n                    <jats:sup>\n                      <jats:bold>111.2<\/jats:bold>\n                    <\/jats:sup>\n                    GL\n                    <jats:sup>\n                      <jats:bold>111.3<\/jats:bold>\n                    <\/jats:sup>\n                    to\n                    <jats:sup>\n                      <jats:bold>111.2<\/jats:bold>\n                    <\/jats:sup>\n                    GW\n                    <jats:sup>\n                      <jats:bold>111.3<\/jats:bold>\n                    <\/jats:sup>\n                    and the introduction of the double GWGW motif into CAP206-CH12 modestly improved neutralization potency (2.5\u20133-fold) but did not reach the levels of potency of VRC42.01, 4E10 or PGZL1. To explore the lack of potency\/breadth, viral mutagenesis was performed to map the CAP206-CH12 epitope. This indicated that CAP206-CH12 is dependent on D\n                    <jats:sup>\n                      <jats:bold>674<\/jats:bold>\n                    <\/jats:sup>\n                    , a highly variable residue at the solvent-exposed elbow of MPER. In contrast, VRC42.01, PGZL1 and 4E10 were dependent on highly conserved residues (W\n                    <jats:sup>\n                      <jats:bold>672<\/jats:bold>\n                    <\/jats:sup>\n                    , F\n                    <jats:sup>\n                      <jats:bold>673<\/jats:bold>\n                    <\/jats:sup>\n                    , T\n                    <jats:sup>\n                      <jats:bold>676<\/jats:bold>\n                    <\/jats:sup>\n                    , and W\n                    <jats:sup>\n                      <jats:bold>680<\/jats:bold>\n                    <\/jats:sup>\n                    ) facing the hydrophobic patch of the MPER. Therefore, while CAP206-CH12, VRC42.01, PGZL1 and 4E10 share germline genes and show some evidence of convergent evolution, their dependence on different amino acids, which impacts orientation of binding to the MPER, result in differences in breadth and potency. These data have implications for the design of HIV vaccines directed at the MPER epitope.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1010450","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T13:42:23Z","timestamp":1662126143000},"page":"e1010450","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dependence on a variable residue limits the breadth of an HIV MPER neutralizing antibody, despite convergent evolution with broadly neutralizing antibodies"],"prefix":"10.1371","volume":"18","author":[{"given":"Cathrine","family":"Scheepers","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prudence","family":"Kgagudi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nonkululeko","family":"Mzindle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elin S.","family":"Gray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thandeka","family":"Moyo-Gwete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bronwen E.","family":"Lambson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent","family":"Oosthuysen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Batsirai","family":"Mabvakure","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nigel J.","family":"Garrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salim S.","family":"Abdool Karim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn","family":"Morris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8719-4028","authenticated-orcid":true,"given":"Penny 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Steichen","year":"2016","journal-title":"Immunity"},{"key":"ppat.1010450.ref010","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1038\/nm.3963","article-title":"Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies","volume":"21","author":"JN Bhiman","year":"2015","journal-title":"Nat Med"},{"key":"ppat.1010450.ref011","first-page":"449","article-title":"Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-","volume":"165","author":"M Bonsignori","year":"2016","journal-title":"Mimic Antibody. 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Soto","year":"2016","journal-title":"PLoS One"},{"key":"ppat.1010450.ref019","first-page":"1","article-title":"Maturation and diversity of the VRC01-antibody lineage over 15 years of chronic HIV-1 infection","volume":"161","author":"X Wu","year":"2015","journal-title":"Cell"},{"key":"ppat.1010450.ref020","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-019-12973-1","article-title":"An MPER antibody neutralizes HIV-1 using germline features shared among donors","volume":"10","author":"L Zhang","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1010450.ref021","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.immuni.2015.12.001","article-title":"Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10","volume":"44","author":"A Irimia","year":"2016","journal-title":"Immunity"},{"key":"ppat.1010450.ref022","doi-asserted-by":"crossref","first-page":"4033","DOI":"10.1128\/JVI.02588-06","article-title":"An affinity-enhanced neutralizing antibody against the membrane-proximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10","volume":"81","author":"JD Nelson","year":"2007","journal-title":"J Virol"},{"key":"ppat.1010450.ref023","doi-asserted-by":"crossref","first-page":"11265","DOI":"10.1128\/JVI.01359-09","article-title":"Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region","volume":"83","author":"ES Gray","year":"2009","journal-title":"J Virol"},{"key":"ppat.1010450.ref024","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0023532","article-title":"Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting","volume":"6","author":"L Morris","year":"2011","journal-title":"PLoS One"},{"key":"ppat.1010450.ref025","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ebiom.2016.08.045","article-title":"Amino Acid Changes in the HIV-1 gp41 Membrane Proximal Region Control Virus Neutralization Sensitivity","volume":"12","author":"T Bradley","year":"2016","journal-title":"EBioMedicine"},{"key":"ppat.1010450.ref026","doi-asserted-by":"crossref","first-page":"4828","DOI":"10.1128\/JVI.00198-11","article-title":"The Neutralization Breadth of HIV-1 Develops Incrementally over Four Years and Is Associated with CD4+ T Cell Decline and High Viral Load during Acute Infection","volume":"85","author":"ES Gray","year":"2011","journal-title":"J Virol"},{"key":"ppat.1010450.ref027","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.immuni.2004.12.011","article-title":"Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41","volume":"22","author":"RMF Cardoso","year":"2005","journal-title":"Immunity"},{"key":"ppat.1010450.ref028","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1128\/JVI.79.2.1252-1261.2005","article-title":"Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1","volume":"79","author":"MB Zwick","year":"2005","journal-title":"J Virol"},{"key":"ppat.1010450.ref029","first-page":"E8892","article-title":"Structure of the membrane proximal external region of HIV-1 envelope glycoprotein","volume":"115","author":"Q Fu","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010450.ref030","doi-asserted-by":"crossref","first-page":"4688","DOI":"10.1128\/JVI.07163-11","article-title":"Two Distinct Broadly Neutralizing Antibody Specificities of Different Clonal Lineages in a Single HIV-1-Infected Donor: Implications for Vaccine Design","volume":"86","author":"M Bonsignori","year":"2012","journal-title":"J Virol"},{"key":"ppat.1010450.ref031","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/COH.0000000000000550","article-title":"Coevolution of HIV-1 and broadly neutralizing antibodies","volume":"14","author":"NA Doria-Rose","year":"2019","journal-title":"Curr Opin HIV AIDS"},{"key":"ppat.1010450.ref032","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.cell.2014.06.022","article-title":"Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies","volume":"158","author":"F Gao","year":"2014","journal-title":"Cell"},{"key":"ppat.1010450.ref033","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12977-018-0443-0","article-title":"Development of broadly neutralizing antibodies in HIV\u20141 infected elite neutralizers","volume":"15","author":"E Landais","year":"2018","journal-title":"Retrovirology"},{"key":"ppat.1010450.ref034","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/JVI.00878-18","article-title":"HIV-1 Subtype C-Infected Children with Exceptional Neutralization Breadth Exhibit Polyclonal Responses Targeting Known Epitopes","volume":"92","author":"Z Ditse","year":"2018","journal-title":"J Virol"},{"key":"ppat.1010450.ref035","doi-asserted-by":"crossref","first-page":"10574","DOI":"10.1128\/JVI.01012-16","article-title":"Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding","volume":"90","author":"NS Longo","year":"2016","journal-title":"J Virol"},{"key":"ppat.1010450.ref036","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1016\/j.immuni.2016.04.016","article-title":"Early Antibody Lineage Diversification and Independent Limb Maturation Lead to Broad HIV-1 Neutralization Targeting the Env High-Mannose Patch","volume":"44","author":"DT MacLeod","year":"2016","journal-title":"Immunity"},{"key":"ppat.1010450.ref037","author":"I Mikell","year":"2012","journal-title":"Evolution of Cross-Neutralizing Antibody Specificities to the CD4-BS and the Carbohydrate Cloak of the HIV Env in an HIV-1-Infected Subject"},{"key":"ppat.1010450.ref038","doi-asserted-by":"crossref","first-page":"11502","DOI":"10.1128\/JVI.05363-11","article-title":"Polyclonal B Cell Responses to Conserved Neutralization Epitopes in a Subset of HIV-1-Infected Individuals","volume":"85","author":"GD Tomaras","year":"2011","journal-title":"J Virol"},{"key":"ppat.1010450.ref039","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1003738","article-title":"Viral Escape from HIV-1 Neutralizing Antibodies Drives Increased Plasma Neutralization Breadth through Sequential Recognition of Multiple Epitopes and Immunotypes","volume":"9","author":"CK Wibmer","year":"2013","journal-title":"PLoS Pathog"},{"key":"ppat.1010450.ref040","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.coviro.2021.09.015","article-title":"Strategies for eliciting multiple lineages of broadly neutralizing antibodies to HIV by vaccination","volume":"51","author":"Z Mu","year":"2021","journal-title":"Curr Opin Virol"},{"key":"ppat.1010450.ref041","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.virol.2020.06.016","article-title":"Selection and immune recognition of HIV-1 MPER mimotopes","volume":"550","author":"L Wieczorek","year":"2020","journal-title":"Virology"},{"key":"ppat.1010450.ref042","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.712122","article-title":"Broadly Neutralizing Antibodies for HIV-1 Prevention","volume":"12","author":"SR Walsh","year":"2021","journal-title":"Front Immunol"},{"key":"ppat.1010450.ref043","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0001954","article-title":"Establishing a cohort at high risk of HIV infection in South Africa: Challenges and experiences of the CAPRISA 002 acute infection study","volume":"3","author":"F van Loggerenberg","year":"2008","journal-title":"PLoS One"},{"key":"ppat.1010450.ref044","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1093\/bioinformatics\/btt593","article-title":"PEAR: A fast and accurate Illumina Paired-End reAd mergeR","volume":"30","author":"J Zhang","year":"2014","journal-title":"Bioinformatics"},{"key":"ppat.1010450.ref045","doi-asserted-by":"crossref","first-page":"2460","DOI":"10.1093\/bioinformatics\/btq461","article-title":"Search and clustering orders of magnitude faster than BLAST","volume":"26","author":"RC Edgar","year":"2010","journal-title":"Bioinformatics"},{"key":"ppat.1010450.ref046","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3389\/fimmu.2016.00372","article-title":"SONAR: A high-throughput pipeline for inferring antibody ontogenies from longitudinal sequencing of B cell transcripts","volume":"7","author":"CA Schramm","year":"2016","journal-title":"Front Immunol"},{"key":"ppat.1010450.ref047","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1093\/bioinformatics\/btv359","article-title":"Change-O: A toolkit for analyzing large-scale B cell immunoglobulin repertoire sequencing data","volume":"31","author":"NT Gupta","year":"2015","journal-title":"Bioinformatics"},{"key":"ppat.1010450.ref048","first-page":"1","article-title":"IMGT\/Highv-quest: The IMGT web portal for immunoglobulin (IG) or antibody and T cell receptor (TR) analysis from NGS high throughput and deep sequencing","volume":"8","author":"E Alamyar","year":"2012","journal-title":"Immunome Res"},{"key":"ppat.1010450.ref049","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1038\/ncomms3333","article-title":"IMGT\/HighV QUEST paradigm for T cell receptor IMGT clonotype diversity and next generation repertoire immunoprofiling","volume":"4","author":"S Li","year":"2013","journal-title":"Nat Commun"},{"key":"ppat.1010450.ref050","first-page":"1695","article-title":"The Igraph Software Package for Complex Network Research","author":"G Csardi","year":"2005","journal-title":"InterJournal"},{"key":"ppat.1010450.ref051","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jim.2007.09.017","article-title":"Efficient generation of monoclonal antibodies from single human B cells by single cell RT-PCR and expression vector cloning","volume":"329","author":"T Tiller","year":"2008","journal-title":"J Immunol Methods"},{"key":"ppat.1010450.ref052","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1126\/science.1207532","article-title":"Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing","volume":"333","author":"X Wu","year":"2011","journal-title":"Science (80-)"},{"key":"ppat.1010450.ref053","article-title":"Evaluating neutralizing antibodies against HIV, SIV, and SHIV in luciferase 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