{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T20:36:16Z","timestamp":1771274176231,"version":"3.50.1"},"reference-count":76,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2016,9,12]],"date-time":"2016-09-12T00:00:00Z","timestamp":1473638400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI091693"],"award-info":[{"award-number":["AI091693"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI104739"],"award-info":[{"award-number":["AI104739"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["OPP1108179"],"award-info":[{"award-number":["OPP1108179"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>An effective preventive vaccine is highly sought after in order to stem the current HIV-1 pandemic. Both conservation of contiguous gp41 membrane-proximal external region (MPER) amino acid sequences across HIV-1 clades and the ability of anti-MPER broadly neutralizing antibodies (BNAbs) to block viral hemifusion\/fusion establish the MPER as a prime vaccination target. In earlier studies, we described the development of an MPER vaccine formulation that takes advantage of liposomes to array the MPER on a lipid bilayer surface, paralleling its native configuration on the virus membrane while also incorporating molecular adjuvant and CD4 T cell epitope cargo. Here we demonstrate that several immunizations with MPER\/liposomes induce high levels of bone marrow long-lived plasma cell (LLPC) antibody production. Single-cell immunoglobulin gene retrieval analysis shows that these plasma cells are derived from a germ line repertoire of B cells with a diverse representation of immunoglobulin genes, exhibiting antigen-driven positive selection. Characterization of LLPC recombinant monoclonal antibodies (rMAbs) indicates that antigen recognition is achieved through convergence on a common epitopic focus by utilizing various complementarity-determining region H3 (CDRH3) lengths. Importantly, the vast majority of rMAbs produced from these cells lack polyreactivity yet manifest antigen specificity in the context of lipids, shaping MPER-specific paratopes through selective pressure. Taken together, these findings demonstrate that the MPER is a vaccine target with minimal risk of generating off-target autoimmunity.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            A useful vaccine must generate desired long-term, antigen-specific antibody responses devoid of polyreactivity or autoreactivity. The common polyreactive features of some HIV-1 BNAbs have raised concern about elicitation of anti-MPER antibodies. Utilizing single-LLPC repertoire analysis and biophysical characterization of anti-MPER rMAbs, we show that their fine specificities require a structural fitness of the antibody combining site involving heavy and light chain variable domains shaped by somatic hypermutation and affinity maturation of B cells in the germinal center. Perhaps more importantly, our results demonstrate that the majority of MPER-specific antibodies are not inherently polyspecific and\/or autoreactive, suggesting that polyreactivity of MPER-specific antibodies is separable from their antigen specificity.\n          <\/jats:p>","DOI":"10.1128\/jvi.01089-16","type":"journal-article","created":{"date-parts":[[2016,7,28]],"date-time":"2016-07-28T02:58:24Z","timestamp":1469674704000},"page":"8875-8890","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":20,"title":["Generation of Long-Lived Bone Marrow Plasma Cells Secreting Antibodies Specific for the HIV-1 gp41 Membrane-Proximal External Region in the Absence of Polyreactivity"],"prefix":"10.1128","volume":"90","author":[{"given":"Luke R.","family":"Donius","sequence":"first","affiliation":[{"name":"Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuxing","family":"Cheng","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaewon","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhen-Yu J.","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry &amp; Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa","family":"Hanson","sequence":"additional","affiliation":[{"name":"Departments of Materials Science and Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Zhang","sequence":"additional","affiliation":[{"name":"Departments of Materials Science and Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Todd M.","family":"Gierahn","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Marquez","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammed","family":"Uduman","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven H.","family":"Kleinstein","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale School of Medicine, New Haven, Connecticut, USA"},{"name":"Department of Immunology, Yale School of Medicine, and Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darrell","family":"Irvine","sequence":"additional","affiliation":[{"name":"Departments of Materials Science and Engineering and Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA"},{"name":"Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA"},{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. Christopher","family":"Love","sequence":"additional","affiliation":[{"name":"Koch Institute for Integrative Cancer Research at MIT, Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellis L.","family":"Reinherz","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"},{"name":"Department of Dermatology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit048"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3516"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12075"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80561"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/aid.1994.10.359"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11544"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02837-13"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023532"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.11.6642-6647.1993"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02588-06"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05312-11"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.22.10892-10905.2001"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3158"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.052"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.3.2469-2480.1999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2013.09.030"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00020-07"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.11.018"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.2154"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901474106"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad2450"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.12.001"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703485200"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.6089-6092.1999"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.2.1209-1218.1995"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0908713106"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.03.067"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004728107"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02257-09"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02113-09"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.19.10724-10737.2004"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2004.12.011"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909680107"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02357-09"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.6.3155-3161.2004"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.1325"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2006.10.088"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2010.06.010"},{"key":"e_1_3_2_40_2","first-page":"3","article-title":"Antigenicity and immunogenicity in HIV-1 antibody-based vaccine design","volume":"8","author":"Kong L","year":"2012","unstructured":"Kong L, Sattentau QJ. 2012. Antigenicity and immunogenicity in HIV-1 antibody-based vaccine design. J AIDS Clin Res S8:3.","journal-title":"J AIDS Clin Res"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027824"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.12.045"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.494609"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.527747"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2009.05.059"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302511"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004073"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20121977"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110363"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.07.003"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1111781"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02378-14"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.40"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2009.08.009"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv359"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks457"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.016"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80541-5"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.05.009"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1210"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2014.02.020"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00250"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1207227"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208984109"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2013.04.012"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187659"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.180.3.885"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.02.022"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219320110"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1301285"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101633"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003639"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01359-09"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00129-15"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01992-08"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-11-44"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.06.013"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01089-16","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01089-16","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T14:12:23Z","timestamp":1646489543000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01089-16"}},"subtitle":[],"editor":[{"given":"F.","family":"Kirchhoff","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,10]]},"references-count":76,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2016,10]]}},"alternative-id":["10.1128\/JVI.01089-16"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01089-16","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10]]},"assertion":[{"value":"2016-06-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-07-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-09-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}