{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:06:51Z","timestamp":1791212811497,"version":"4.1.0"},"reference-count":51,"publisher":"Frontiers Media SA","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2014.00398","type":"journal-article","created":{"date-parts":[[2014,8,28]],"date-time":"2014-08-28T04:56:09Z","timestamp":1409201769000},"source":"Crossref","is-referenced-by-count":14,"title":["The Antibody Germline\/Maturation Hypothesis, Elicitation of Broadly Neutralizing Antibodies Against HIV-1 and Cord Blood IgM Repertoires"],"prefix":"10.3389","volume":"5","author":[{"given":"Ponraj","family":"Prabakaran","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weizao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimiter S.","family":"Dimitrov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2014,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1038\/31514","article-title":"The antigenic structure of the HIV gp120 envelope glycoprotein","volume":"393","author":"Wyatt","year":"1998","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1126\/science.1245625","article-title":"Crystal structure of a soluble cleaved HIV-1 envelope trimer","volume":"342","author":"Julien","year":"2013","journal-title":"Science"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1126\/science.1245627","article-title":"Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer","volume":"342","author":"Lyumkis","year":"2013","journal-title":"Science"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1405","DOI":"10.1586\/14760584.7.9.1405","article-title":"Viral sequence diversity: challenges for AIDS vaccine designs","volume":"7","author":"McBurney","year":"2008","journal-title":"Expert Rev Vaccines"},{"key":"B5","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1038\/nature01470","article-title":"Antibody neutralization and escape by HIV-1","volume":"422","author":"Wei","year":"2003","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"7385","DOI":"10.1073\/pnas.0811427106","article-title":"Examination of the contributions of size and avidity to the neutralization mechanisms of the anti-HIV antibodies b12 and 4E10","volume":"106","author":"Klein","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B7","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1038\/nature01188","article-title":"HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites","volume":"420","author":"Kwong","year":"2002","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/ni0304-233","article-title":"HIV vaccine design and the neutralizing antibody problem","volume":"5","author":"Burton","year":"2004","journal-title":"Nat Immunol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/nature12053","article-title":"Extensive maturation of cross-reactive HIV-1 neutralizing antibodies but not of neutralizing antibodies against the SARS CoV, Nipah and Hendra viruses","volume":"P10-18","author":"Chen","year":"2007","journal-title":"AIDS Vaccine"},{"key":"B10","first-page":"11","article-title":"All known cross reactive HIV-1 neutralizing antibodies are highly divergent from germline and their elicitation may require prolonged periods of time","volume":"24","author":"Chen","year":"2008","journal-title":"AIDS Res Hum Retroviruses"},{"key":"B11","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/j.bbrc.2009.09.029","article-title":"Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens","volume":"390","author":"Xiao","year":"2009","journal-title":"Biochem Biophys Res Commun"},{"key":"B12","article-title":"Identification of non-HIV immunogens that bind to germline b12 predecessors and elicit cross-reactive neutralizing HIV-1 antibodies","volume-title":"AIDS","author":"Yang","year":"2014"},{"key":"B13","doi-asserted-by":"publisher","first-page":"802","DOI":"10.3390\/v1030802","article-title":"Maturation pathways of cross-reactive HIV-1 neutralizing antibodies","volume":"1","author":"Xiao","year":"2009","journal-title":"Viruses"},{"key":"B14","doi-asserted-by":"publisher","first-page":"347","DOI":"10.4161\/mabs.2.3.11779","article-title":"Therapeutic antibodies, vaccines and antibodyomes","volume":"2","author":"Dimitrov","year":"2010","journal-title":"MAbs"},{"key":"B15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3389\/fmicb.2012.00277","article-title":"Origin, diversity, and maturation of human antiviral antibodies analyzed by high-throughput sequencing","volume":"3","author":"Prabakaran","year":"2012","journal-title":"Front Microbiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1111\/imr.12075","article-title":"HIV-1 neutralizing antibodies: understanding nature\u00e2\u20ac\u2122s pathways","volume":"254","author":"Mascola","year":"2013","journal-title":"Immunol Rev"},{"key":"B17","first-page":"1","article-title":"Paradigm changes and the future of HIV vaccine research: a summary of a workshop held in Baltimore on 20 November 2013","volume":"5","author":"Van Regenmortel","year":"2014","journal-title":"J AIDS Clin Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1007\/978-1-59745-554-1_6","article-title":"Construction of a large naive human phage-displayed Fab library through one-step cloning","volume":"525","author":"Zhu","year":"2009","journal-title":"Methods Mol Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00251-011-0595-8","article-title":"Expressed antibody repertoires in human cord blood cells: 454 sequencing and IMGT\/HighV-QUEST analysis of germline gene usage, junctional diversity, and somatic mutations","volume":"64","author":"Prabakaran","year":"2012","journal-title":"Immunogenetics"},{"key":"B20","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1007\/978-1-61779-842-9_32","article-title":"IMGT((R)) tools for the nucleotide analysis of immunoglobulin (IG) and T cell receptor (TR) V-(D)-J repertoires, polymorphisms, and IG mutations: IMGT\/V-QUEST and IMGT\/HighV-QUEST for NGS","volume":"882","author":"Alamyar","year":"2012","journal-title":"Methods Mol Biol"},{"key":"B21","first-page":"95","article-title":"BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95\/98\/NT","volume":"41","author":"Hall","year":"1999","journal-title":"Nucl Acids Symp Ser"},{"key":"B22","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1186\/1471-2105-10-356","article-title":"phyloXML: XML for evolutionary biology and comparative genomics","volume":"10","author":"Han","year":"2009","journal-title":"BMC Bioinformatics"},{"key":"B23","doi-asserted-by":"publisher","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":"Wu","year":"2011","journal-title":"Science"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1126\/science.1207227","article-title":"Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding","volume":"333","author":"Scheid","year":"2011","journal-title":"Science"},{"key":"B25","doi-asserted-by":"publisher","first-page":"250","DOI":"10.3389\/fimmu.2014.00250","article-title":"Immunologic basis for long HCDR3s in broadly neutralizing antibodies against HIV-1","volume":"5","author":"Yu","year":"2014","journal-title":"Front Immunol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e1003106","DOI":"10.1371\/journal.ppat.1003106","article-title":"Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs","volume":"9","author":"Hoot","year":"2013","journal-title":"PLoS Pathog"},{"key":"B27","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1084\/jem.20122824","article-title":"Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies","volume":"210","author":"McGuire","year":"2013","journal-title":"J Exp Med"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2645","DOI":"10.1128\/JVI.03228-13","article-title":"Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D","volume":"88","author":"McGuire","year":"2014","journal-title":"J Virol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1038\/nature12053","article-title":"Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus","volume":"496","author":"Liao","year":"2013","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature13036","article-title":"Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies","volume":"509","author":"Doria-Rose","year":"2014","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1126\/science.1234150","article-title":"Rational HIV immunogen design to target specific germline B cell receptors","volume":"340","author":"Jardine","year":"2013","journal-title":"Science"},{"key":"B32","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1016\/j.cell.2013.03.018","article-title":"Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization","volume":"153","author":"Klein","year":"2013","journal-title":"Cell"},{"key":"B33","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.immuni.2013.04.012","article-title":"Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies","volume":"39","author":"Zhou","year":"2013","journal-title":"Immunity"},{"key":"B34","doi-asserted-by":"publisher","first-page":"6470","DOI":"10.1073\/pnas.1219320110","article-title":"Mining the antibodyome for HIV-1-neutralizing antibodies with next-generation sequencing and phylogenetic pairing of heavy\/light chains","volume":"110","author":"Zhu","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B35","doi-asserted-by":"publisher","first-page":"E4088","DOI":"10.1073\/pnas.1306262110","article-title":"De novo identification of VRC01 class HIV-1-neutralizing antibodies by next-generation sequencing of B-cell transcripts","volume":"110","author":"Zhu","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e1003754","DOI":"10.1371\/journal.ppat.1003754","article-title":"The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies","volume":"9","author":"Sok","year":"2013","journal-title":"PLoS Pathog"},{"key":"B37","doi-asserted-by":"publisher","first-page":"11401","DOI":"10.1128\/JVI.05312-11","article-title":"Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a patient with 2F5-like antibodies","volume":"85","author":"Zhu","year":"2011","journal-title":"J Virol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2426","DOI":"10.1128\/JVI.02837-13","article-title":"Structural basis for HIV-1 neutralization by 2F5-like antibodies m66 and m66.6","volume":"88","author":"Ofek","year":"2014","journal-title":"J Virol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1038\/nm.3565","article-title":"Early development of broadly neutralizing antibodies in HIV-1-infected infants","volume":"20","author":"Goo","year":"2014","journal-title":"Nat Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"20216","DOI":"10.1073\/pnas.0909775106","article-title":"Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire","volume":"106","author":"Glanville","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B41","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S1074-7613(00)80108-9","article-title":"Junctional amino acids determine the maturation pathway of an antibody","volume":"11","author":"Furukawa","year":"1999","journal-title":"Immunity"},{"key":"B42","doi-asserted-by":"publisher","first-page":"E2083","DOI":"10.1073\/pnas.1208984109","article-title":"Structural basis for germ-line gene usage of a potent class of antibodies targeting the CD4-binding site of HIV-1 gp120","volume":"109","author":"West","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1567","DOI":"10.1084\/jem.20052217","article-title":"Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production","volume":"203","author":"Ippolito","year":"2006","journal-title":"J Exp Med"},{"key":"B44","doi-asserted-by":"publisher","first-page":"8409","DOI":"10.4049\/jimmunol.181.12.8409","article-title":"Preferential use of DH reading frame 2 alters B cell development and antigen-specific antibody production","volume":"181","author":"Schelonka","year":"2008","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0092-8674(91)90406-O","article-title":"B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D mu protein and selection of DH element reading frames","volume":"65","author":"Gu","year":"1991","journal-title":"Cell"},{"key":"B46","doi-asserted-by":"publisher","first-page":"5567","DOI":"10.4049\/jimmunol.1201929","article-title":"The restricted DH gene reading frame usage in the expressed human antibody repertoire is selected based upon its amino acid content","volume":"190","author":"Benichou","year":"2013","journal-title":"J Immunol"},{"key":"B47","doi-asserted-by":"publisher","first-page":"8416","DOI":"10.4049\/jimmunol.181.12.8416","article-title":"Regulation of repertoire development through genetic control of DH reading frame preference","volume":"181","author":"Zemlin","year":"2008","journal-title":"J Immunol"},{"key":"B48","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/nbt.2782","article-title":"The promise and challenge of high-throughput sequencing of the antibody repertoire","volume":"32","author":"Georgiou","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1038\/nbt.2197","article-title":"B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study","volume":"30","author":"Haynes","year":"2012","journal-title":"Nat Biotechnol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2014.05.010","article-title":"Immunogen design for HIV-1 and influenza","author":"Rathore","year":"2014","journal-title":"Biochim Biophys Acta"},{"key":"B51","doi-asserted-by":"publisher","first-page":"18214","DOI":"10.1073\/pnas.1317855110","article-title":"Recognition of synthetic glycopeptides by HIV-1 broadly neutralizing antibodies and their unmutated ancestors","volume":"110","author":"Alam","year":"2013","journal-title":"Proc Natl Acad Sci U S A"}],"container-title":["Frontiers in Immunology"],"original-title":[],"deposited":{"date-parts":[[2015,2,18]],"date-time":"2015-02-18T15:28:37Z","timestamp":1424273317000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fimmu.2014.00398\/abstract"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,28]]},"references-count":51,"URL":"https:\/\/doi.org\/10.3389\/fimmu.2014.00398","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,28]]}}}